Morphinan derivative and its pharmaceutical applications

ABSTRACT

A morphinan derivative or its pharmacologically allowed acid addition salt represented with compound I,                    
     an analgesic and diuretic having its derivative or its salt as the active ingredient, and its production process are described. The compound of the present invention possesses strong analgesic activity and diuretic action as a highly selective κ-opioid agonist, allowing it to be used as a useful analgesic and diuretic.

This is a 371 of PCT/JP93/00080, filed Jan. 22, 1993.

TECHNICAL FIELD

The present invention relates to an analgesic and diuretic having as itsactive ingredient a morphinan derivative or a pharmacologicallyacceptable acid salt thereof.

BACKGROUND ART

Morphine has long been known as a powerful analgesic having a morphinanskeleton, and is widely used even at present. However, this drug hasserious side effects that present clinical problems, including drugdependence, action that suppresses respiration and action thatsuppresses smooth muscle movement (constipation). Thus, there is a needfor a powerful analgesic that acts on the central nervous system andthat also can be used safely.

In addition, it has also been reported that drugs that act on opioidreceptors effect urination (J. D. Leander, J. Pharmacol. Exp. Ther.,227, 35 (1983)), and thus, the effective use of that action is alsodesired.

DISCLOSURE OF THE INVENTION

The existence of opioid receptors has been clearly established asreceptors involved in analgesic action on the central nervous system.Moreover, these receptors are known to be able to classified into thethree types, μ, δ and κ. In addition, σ receptors are also known todemonstrate psychotomimetics. Those agonists having affinity for theseκ-receptors or δ-receptors have been shown to have strong analgesicactivity, while not demonstrating serious side effects that presentclinical problems, such as drug dependence, action that suppressesrespiration and action that suppresses smooth muscle movement, that areobserved in the case of morphin and so forth, which are μ-receptoragonists. In addition, the psychotomimetics observed in existingκ-receptor agonists are reported to be caused by the affinity toσ-receptors. Moreover, κ-receptor agonists do not demonstrate crosstolerance with μ-receptor agonists such as morphine. Analgesics free ofsuch side effects have a high degree of usefulness since they can beapplied in not only the control of pain in patients havingpost-operative pain and cancer patients suffering from cancer, but canalso be widely applied for general pain. In addition, the absence ofcross tolerance indicates that these analgesics are effective even inpatients that have developed tolerance to analgesics such as morphin.Therefore, the object of the present invention is to provide aκ-receptor agonist or δ-receptor agonist that has powerful analgesicaction while not having serious side effects like those of morphin, nothaving cross tolerance with morphin and so forth, and not demonstratingany affinity whatsoever for σ-receptors. In addition, another object ofthe present invention is to provide a useful diuretic that takesadvantage of the effects of opioid action drugs on urination.

As a result of earnest studies to solve the above-mentioned problems,the inventors of the present invention found that the morphinanderivatives indicated by the below formula (I) is a compound thatdemonstrates analgesic action and diuretic action having the excellentcharacteristics described above, thus leading to completion of thepresent invention.

Namely, the present invention relates to a morphinan derivativerepresented with general formula (I) below or pharmacologicallyacceptable acid salt thereof, its production process as well as itspharmaceutical applications:

[wherein, represents a single or double bond; R¹ represents an alkylgroup having 1-5 carbon atoms, a cycloalkylalkyl group having 4-7 carbonatoms, a cycloalkenylalkyl group having 5-7 carbon atoms, an aryl grouphaving 6-12 carbon atoms, an aralkyl group having 7-13 carbon atoms, analkenyl group having 4-7 carbon atoms, an allyl group, a furan-2-ylalkylgroup having 1-5 carbon atoms, or a thiophen-2-ylalkyl group having 1-5carbon atoms; R² represents a hydrogen atoms, a hydroxy group, a nitrogroup, an alkanoyloxy group having 1-5 carbon atoms, an alkoxy grouphaving 1-5 carbon atoms, an alkyl group having 1-5 carbon atoms, or—NR⁹R¹⁰ wherein R⁹ represents a hydrogen atom or an alkyl group having1-5 carbon atoms, and R¹⁰ represents a hydrogen atom, an alkyl grouphaving 1-5 carbon atoms, or —C(═O)R¹¹ wherein R¹¹ represents a hydrogenatom, a phenyl group or an alkyl group having 1-5 carbon atoms; R³represents a hydrogen atom, a hydroxy group, an alkanoyloxy group having1-5 carbon atoms, or an alkoxy group having 1-5 carbon atoms; Arepresents —XC(═Y)—, —XC(═Y)Z—, —X—, —XSO₂—, or —OC(OR⁴)R⁴— (where, X Yand Z each independently represent NR₄, S or O wherein R⁴ represents ahydrogen atom, a straight-chain or branched chain alkyl group having 1-5carbon atoms or an aryl group having 6-12 carbon atoms, and wherein R⁴may be identical or different); B represents a valence bond, astraight-chain or branched chain alkylene group having 1-14 carbon atoms(which may be substituted with at least one type of substituent groupsselected from the group consisting of an alkoxy group having 1-5 carbonatoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group,fluorine, chlorine, bromine, iodine, an amino group, a nitro group, acyano group, a trifluoromethyl group and a phenoxy group, and wherein 1to 3 methylene groups may be replaced with carbonyl groups), an acyclicunsaturated hydrocarbon containing from 1 to 3 double bonds and/ortriple bonds and having 2-14 carbon atoms (which may be substituted withat least one substituent group selected from the group consisting of analkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5carbon atoms, a hydroxy group, fluorine, chlorine, bromine, iodine, anamino group, a nitro group, a cyano group, a trifluoromethyl group and aphenoxy group, and wherein from 1 to 3 methylene groups may be replacedwith carbonyl groups), or a straight-chain or branched chain saturatedor unsaturated hydrocarbon group containing from 1 to 5 thioether, etherand/or amino bonds and having 1-14 carbon atoms (wherein hetero atomsare not bonded directly to A, and 1 to 3 methylene groups may bereplaced with carbonyl groups); R⁵ represents a hydrogen atom or anorganic group having the basic skeleton of (formula 1) (which may besubstituted with at least one or more substituent groups selected fromthe group consisting of an alkyl group having 1-5 carbon atoms, analkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5carbon atoms, a hydroxy group, fluorine, chlorine, bromine, iodine, anamino group, a nitro group, a cyano group, an isothiocyanate group, atrifluoromethyl group and a methylenedioxy group),

(Formula 1) Organic Group Represented by R⁵ (Formula 1-1) R⁶ representsa hydrogen atom; R⁷ represents a hydrogen atom, a hydroxy group, analkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5carbon atoms, or R⁶ and R⁷ together represent —O—, —CH₂— or —S—; R⁸represents a hydrogen atom, an alkyl group having 1-5 carbon atoms, oran alkanoyl group having 1-5 carbon atoms, and the general formula (I)includes the (+) form, (−) form and (±) form].

DETAILED DESCRIPTION

Here, preferable examples of R¹ include an alkyl group having 1-5 carbonatoms, a cycloalkylmethyl group having 4-7 carbon atoms, acycloalkenylmethyl group having 5-7 carbon atoms, a phenylalkyl grouphaving 7-13 carbon atoms, an alkenyl group having 4-7 carbon atoms, anallyl group, a furan-2-yl-alkyl group having 1-5 carbon atoms and athiophen-2-yl-alkyl group having 1-5 carbon atoms, while particularlypreferable examples of R¹ include methyl, ethyl, cyclopropylmethyl,cyclobutylmethyl, cyclopentylmethyl, cyclopentenylmethyl,cyclohexenylmethyl, benzyl, phenethyl, trans-2-butenyl,2-methyl-2-butenyl, allyl, furan-2-yl-methyl and thiophen-2-yl-methylgroups.

Preferable examples of R² include a hydrogen atom, and hydroxy, nitro,acetoxy, methoxy, methyl, ethyl, propyl, amino, dimethylamino,acetylamino and benzoylamino groups, while particularly preferableexamples include a hydrogen atom, and hydroxy, nitro, acetoxy, methyland dimethylamino groups.

Preferable examples of R³ include a hydrogen atom, and hydroxy, acetoxyand methoxy groups.

Preferable examples of A include —NR⁴C(═O)—, —NR⁴C(═S)—, —NR⁴C(═O)O—,—NR⁴C(═O)NR⁴—, —NR⁴C(═S)NR⁴—, —NR⁴C(═O)S—, —OC(═O)—, —OC(═O)O—,—SC(═O)—, —NR₄—, —O—, —NR⁴SO₂— and —OSO₂—, while particularly preferableexamples include —NR⁴C(═O)—, —NR⁴C(═S)—, —NR⁴C(═O)O—, —NR⁴C(═O)NR⁴—,—NR⁴C(═S)NR⁴— and —NR⁴SO₂—.

Preferable examples of R⁴ include a hydrogen atom, a straight-chain orbranched alkyl group having 1-5 carbon atoms and a phenyl group, whileparticularly preferable examples include a straight-chain or branchedalkyl group having 1-5 carbon atoms, and particularly methyl, ethyl,propyl, isopropyl, butyl and isobutyl groups.

Preferable examples of B include —(CH₂)n— (n=0-6), —(CH₂)n—C(═O)—(n=1-4), —CH═CH—(CH₂)n— (n=0-4), —C≡C— (CH₂)n— (n=0-4), —CH₂—O—,—CH₂—S—, —CH₂O—(CH₂)₂—O—(CH₂)₂—, —CH₂—O—CH₂—NH—CH₂—O—CH₂— and—CH₂—O—CH₂—S—CH₂—O—CH₂—, while particularly preferable examples include—(CH₂)n— (n=0-6), —CH═CH—(CH₂)n— (n=0-4), —C≡C—(CH₂)n— (n=0-4), —CH₂—O—and —CH₂—S—. Preferable examples of R⁵ include a hydrogen atom and anorganic group having the basic skeleton indicated in (formula 1-1)(which may be substituted with at least one or more substituent groupsselected from the group consisting of an alkyl group having 1-5 carbonatoms, an alkoxy group having 1-5 carbon atoms, an alkanoyloxy grouphaving 1-5 carbon atoms, a hydroxy group, fluorine, chlorine, bromine,an amino group, a nitro group, a cyano group, an isothiocyanate groupand a trifluoromethyl group),

while particularly preferable examples include, a hydrogen atom andphenyl, 3,4-dichlorophenyl, 4-chlorophenyl, 3-chlorophenyl,3,4-difluorophenyl, 4-fluorophenyl, 3-fluorophenyl, 2-fluorophenyl,4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-nitrophenyl,3-nitrophenyl, 2-nitrophenyl, 4-trifluoromethylphenyl,3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 4-methylphenyl,3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 3-methoxyphenyl,2-methoxy, 3-furanyl, 2-furanyl, 3-thienyl, 2-thienyl, cyclopentyl andcyclohexyl groups. But naturally the present invention is not limited tothese examples.

Preferable examples of pharmacologically preferable acid addition saltsinclude, but are naturally not limited to, inorganic acid salts such ashydrochloride, sulfate, nitrate, hydrobromide, hydroiodide andphosphate; organic carboxylates such as acetate, lactate, citrate,oxalate, glutarate, malate, tartrate, fumarate, mandelate, benzoate andphthalate; and, organic sulfonates such as methanesulfonate,ethanesulfonate, benzenesulfonate, p-toluenesulfonate andcamphorsulfonate, while particularly preferable examples includehydrochloride, hydrobromate, phosphate, tartrate and methanesulfonate.

Among the compounds of the general formula (I) of the present invention,compound 1

wherein is a single bond, R¹ is a cyclopropylmethyl group, R² and R³ arehydroxy groups, A is α—NR⁴C(═O)—, R⁴ is a methyl group, B is —CH₂—, R⁵is 3,4-dichlorophenyl, R⁶ and R⁷ are together —O— and R⁸ is a hydrogenatom is named17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylacetamide)morphinan.

In accordance with the above nomenclature system, concrete examples ofthe compound of the present invention are as follows:

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmetyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetoamido)morphinan,

17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-14β-actoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,

17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylcinamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmetyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,

17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmetyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylphenylmethanesulfonamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-metyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylcinnamamido)morphinan,17-metyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-metyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,

17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmetyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)mophinane,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,

17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylcinnamarido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,

17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,

17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6a-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6a-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-metylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5β-epoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-allyl-4,5β-epoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5-α-epoxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,

17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5β-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,

17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methylcinnanamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methylbenzyloxycarbamido)morphinan,17-phenethyl-4,5β-epoxy-3,14β-diacetoxy-6β-(N-methylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diiydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylcinnainamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,

17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,

17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylcinnarnamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3,4-dichlorophenylacetamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylbenzyloxycarbamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutylphenylmethanesulfonamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorobenzamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorobenzamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-dichlorobenzamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-dichlorobenzamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-ethyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-ethyl-3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-ethyl-3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-ethyl-3,4-dichlorophenylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-phenylpropionamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-phenylpropionamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-phenylpropionamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-phenylpropionamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(5-chlorobenzo[b]thienyl)acetamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(5-chlorobenzo[b]thienyl)acetamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(5-chlorobenzo[b]thienyl)acetamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(5-chlorobenzo[b]thienyl)acetamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylphenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylphenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylphenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylphenylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylcyclohexylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylcyclohexylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylcyclohexylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylcyclohexylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-bromophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-bromophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-bromophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-bromophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-benzo[b]thienylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-benzo[b]thienylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-benzo[b]thienylacetamido)morphinan,17-allyl-4,55α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-benzo[b]thienylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorocinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorocinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-dichlorocinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-dichlorocinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-bromophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-bromophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-bromophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-bromophenylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[(R)-N-methyl-2-phenylpropionamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[(R)-N-methyl-2-phenylpropionamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(R)-N-methyl-2-phenylpropionamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(R)-N-methyl-2-phenylpropionamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[(R)-N-methylmethoxyphenylacetamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[(R)-N-methylmethoxyphenylacetamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(R)-N-methylmethoxyphenylacetamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(R)-N-methylmethoxyphenylacetamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[(S)-N-methylmethoxyphenylacetamido]morphinan,17-allyl-4,5a-epoxy-3,14β-dihydroxy-6α-[(S)-N-methylmethoxyphenylacetamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(S)-N-methylmethoxyphenylacetamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(S)-N-methylmethoxyphenylacetamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(3,4-dichlorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(3,4-dichlorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(3,4-dichlorophenylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-difluorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-difluorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-difluorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-difluorophenylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylphenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylphenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylphenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylphenylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[(S)-N-methyl-2-phenylpropionamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[(S)-N-methyl-2-phenylpropionamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(S)-N-methyl-2-phenylpropionamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(S)-N-methyl-2-phenylpropionamido]morphinan,17-cyclopropylmethyl-4,4α-epoxy-3,14β-dihydroxy-6α-[N-methyl-N-2-(3,4-dichlorophenyl)ethylamino]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-N-2-(3,4-dichlorophenyl)ethylamino]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-N-2-(3,4-dichlorophenyl)ethylamino]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-N-2-(3,4-dichlorophenyl)ethylamino]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-nitrophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-nitrophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-nitrophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-nitrophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-aminophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-aminophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-aminophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-aminophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylcyclohexylcarboxyamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylcyclohexylcarboxyamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylcyclohexylcarboxyamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylcyclohexylcarboxyamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylbenzamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylbenzamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylbenzamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylbenzamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-phenylbutyroamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-phenylbutyroamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-phenylbutyroamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-phenylbutyroamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-bromophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-bromophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-bromophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-bromophenylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-6-phenylhexanamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-6-phenylhexanamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-6-phenylhexanamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-6-phenylhexanamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-fluorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-fluorophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-fluorophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-fluorophenylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-N′-(3,4-dichlorophenyl)ureido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-N′-(3,4-dichlorophenyl)ureido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-N′-(3,4-dichlorophenyl)ureido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-N′-(3,4-dichlorophenyl)ureido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-N′-benzylureido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-N′-benzylureido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-N′-benzylureido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-N′-benzylureido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-nitrophenylacetamido)morphinan,

17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-nitrophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-nitrophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-nitrophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-pyridylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-pyridylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-pyridylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-pyridylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-thienyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-thienyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-thienyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-thienyl)acrylamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylthiophenoxyacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylthiophenoxyacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylthiophenoxyacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylthiophenoxyacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylphenoxyacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylphenoxyacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylphenoxyacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylphenoxyacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-nitrobenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-nitrobenzyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-nitrobenzyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-nitrobenzyloxycarbamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-pyridylmethoxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-pyridylmethoxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-pyridylmethoxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-pyridylmethoxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylmethane-sulfonamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylmethane-sulfonamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-dichlorophenylmethanesulfonamido)morphinan,

17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-dichlorophenylmethanesulfonamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-N′-benzylthioureido)morphinan,17-ally-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-N′-benzylthioureido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-N′-benzylthioureido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-N-methyl-N′-benzylthioureido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylhexanamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylhexanamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylhexanamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylhexanamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylheptanamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylheptanamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylheptanamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylheptanamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-aminophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-aminophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-aminophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-aminophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-pyridylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-pyridylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-pyridylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-pyridylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(3-pyridyl)propionamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(3-pyridyl)propionamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(3-pyridyl)propionamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(3-pyridyl)propionamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(3-phenylpropioyloxy)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(3-phenylpropioyloxy)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(3-phenylpropioyloxy)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(3-phenylpropioyloxy)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[2-(3-furyl)ethenylsulfonyloxy]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[2-(3-furyl)ethenylsulfonyloxy]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[2-(3-furyl)ethenylsulfonyloxy]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[2-(3-furyl)ethenylsulfonyloxy]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,

17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-4-trifluoromethyl-cinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxyr-14β-acetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-htydroxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,

17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,

17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-149-hydroxy-6a-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,

17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamiamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3-phenylpropionamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3-trifluoromethyl-cinnamamido)morphinan,17-methyl-4,5a-epoxy-3-methoxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,

17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,55α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3,149-dihydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamainido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinncmamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,

17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphiran,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,

17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,

17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphin,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluorcmethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methlyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,

17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,15α-epoxy-3-methoxy-14β-acetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,

17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,149-diacetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,

17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,

17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,

17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,

17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylainido]morphinan,

17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,

17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,

17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,

17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5β-epoxy-3-acetoxy-14β-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6f-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5a-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5β-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,

17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,

17-phenethyl-4,5α-epoxy-3-hydroxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,

17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido)morphinan,17-methyl-4,5β-epoxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,

17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,

17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-methoxy-14β-acetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-ally-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-acetoxy-14β-hydroxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5β-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-isobutyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5(-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-4-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3-phenylpropiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-cyclohexylpropionamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-cyclohexylpropionamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-cyclohexylpropionamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-cyclohexylpropionamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6a-(N-methylbutyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylbutyloxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylbutyloxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylbutyloxycarbamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-isothiocyanatophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-isothiocyanatophenylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-isothiocyanatophenylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-isothiocyanatophenylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-hexenamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-hexenamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-hexenamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-hexenamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-fluorocinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-fluorocinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-fluorocinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-fluorocinnamamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methoxycinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-methoxycinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methoxycinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methoxycinnamamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-cyclopentylpropionamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-cyclopentylpropionamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-cyclopentylpropionamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-cyclopentylpropionamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-naphthamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-naphthamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-naphthamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-naphthamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-nitrocinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-nitrocinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14α-dihydroxy-6β-(N-methyl-3-nitrocinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-nitrocinnamamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-methoxyethoxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-methoxyethoxycarbamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-methoxyethoxycarbamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-methoxyethoxycarbamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-trans-3-cyclohexylacrylamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-trans-3-cyclohexylacrylamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-trans-3-cyclohexylacrylamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-trans-3-cyclohexylacrylamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylbenzoylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylbenzoylacetamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylbenzoylacetamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylbenzoylacetamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(2-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(2-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(2-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(2-furyl)acrylamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-2-trifluoromethylcinnamamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-isothiocyanatocinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-isothiocyanatocinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-isothiocyanatocinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-isothiocyanatocinnamamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-methylcinnamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan, 17-methyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-[N-methyl-3-(4-trifluoromethyl-phenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14α-dihydroxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,

17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6α-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14i-acetoxy-3-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6f-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14g-acetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5-epoxy-3,14β-diacetoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-hydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-acetoxy-3-methoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-14β-hydroxy-3-acetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3,14g-diacetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-(N-isobutyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-diacetoxy-6β-[N-isobutyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(3-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(3-trifluoromethylphenyl)propiolamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(3-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(3-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(2-thienyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(2-thienyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(2-thienyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(2-thienyl)acrylamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-methyl-4,5α-epoxy-3-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-6α-[N-methyl-trans-3-(3-furyl)-acrylamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14-nitro-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-allyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-phenethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-allyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,14β,17-dimethyl-4,5α-epoxy-3-hydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,14β,17-dimethyl-4,5α-epoxy-3-hydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,14β,17-dimethyl-4,5α-epoxy-3-hydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,14β,17-dimethyl-4,5α-epoxy-3-hydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,

17-phenethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-3,14β-dihydroxy-6α-[N-ethyl-trans-3-(3-furyl)acrylamido]morphinan,

17-allyl-3,14β-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-3,14β-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-3,14β-dihydroxy-4-irethoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-4-methoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-4-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-4-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-3,14β-dihydroxy-4-methoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-3,14β-dihydroxy-4-methoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-3,14β-dihydroxy-4-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,

17-allyl-3,14β-dihydroxy-4-methoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-3,14β-dihydroxy-4-methoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-3,14β-dihydroxy-4-methoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-3,14β-dihydroxy-4-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,

17-methyl-3,14β-dihydroxy-4-methoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-3,14β-dihydroxy-4-methoxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-3,14β-dihydroxy-4-methoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-phenethyl-3,14β-dihydroxy-4-methoxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-3,14β-dihydroxy-4-methoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6α-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3,14β-dihydroxy-59-methyl-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-5s-methyl-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,5β,17-dimethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,5β,17-dimethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,5β,17-dimethyl-4,5α-epoxy-3,14-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,5β,17-dimethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,

17-cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-methyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5a-epoxy-3-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamdo)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-allyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-141-nitro-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-phenethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-nitro-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,

17-allyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-phenethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-dimethylamino-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

14β,17-dimethyl-4,5α-epoxy-3-hydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,14β,17-dimethyl-4,5α-epoxy-3-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,14β,17-dimethyl-4,5α-epoxy-3-hydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,14β,17-dimethyl-4,5α-epoxy-3-hydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-(N-methyl-3-methylcinnamamido)morphinan,

17-phenethyl-4,5α-epoxy-3-hydroxy-14β-methyl-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido)morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-3,14β-dihydroxy-61-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-methyl-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,

17-methyl-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-3,4β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-3,14β-dihydroxy-4-methoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-4-methoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-4-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-3,14β-dihydroxy-4-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-3,14β-dihydroxy-4-methoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-3,14β-dihydroxy-4-methoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-3,14β-dihydroxy-4-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-3,14β-dihydroxy-4-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-methyl-3,14β-dihydroxy-4-methoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-3,14β-dihydroxy-4-methoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-methyl-3,14β-dihydroxy-4-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-3,14β-dihydroxy-4-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-3,14β-dihydroxy-4-methoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-3,14β-dihydroxy-4-methoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-phenethyl-3,14β-dihydroxy-4-methoxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-3,14β-dihydroxy-4-methoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-4,15α-epoxy-3,14β-dihydroxy-5β-methyl-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-allyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6β-(N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,5β,17-dimethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,5β,17-dimethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,5β,17-dimethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,

5β,17-dimethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6β-(N-methyl-3-methylcinnamamido)morphinan,17-phenethyl-4,5α-epoxy-3,14β-dihydroxy-5β-methyl-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,

17-cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-allyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-allyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-allyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-allyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,

17-methyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-methyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamnido]morphinan,17-methyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,17-methyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan,17-phenethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan,17-phenethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan,17-phenethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3-methylcinnamamido)morphinan,and17-phenethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan.

However, the present invention is not limited to these examples.Furthermore, the compounds of the present invention include the (+), (−)and (+) forms.

The compounds of general formula (I) of the present invention can beobtained, specifically, according to the methods described below.

Among the compounds represented by the general formula (I) of thepresent invention, those wherein A is —XC(═Y)—, —XC(═Y)Z— or —XSO₂—(wherein X represents NR₄ or O, Y represents O or S, Z represents O, NHor S, and R⁴ is the same as previously defined) can be obtained,specifically, according to the methods described below.

In general, as shown in Chart 1, said compounds can be obtained bycondensing a carboxylic acid derivative represented by the generalformula (III) (wherein B and R⁵ are the same as previously defined), aformic acid derivative represented by the general formula (IV) (whereinZ, B and R⁵ are the same as previously defined), an isocyanic acid orisothiocyanic acid derivative represented by the general formula (V)(wherein B and R⁵ are the same as previously defined) or a sulfonic acidderivative represented by the general formula (VI) (wherein B and R⁵ arethe same as previously defined), with a 6-amino or 6-hydroxy compoundrepresented by the general formula (II) (wherein R¹, R², R³, R⁶, R⁷ andR⁸ are the same as previously defined, and E represents NHR⁴ (wherein R⁴is the same as previously defined) or OH).

The 6-amino and 6-hydroxy compound used in this condensation can beobtained, specifically, by the process described below.

As shown in Chart 2, a 6α-amino compound represented by the generalformula (IIaα1) (wherein R¹, R², R³, R⁶, R⁷ and R⁸ are the same aspreviously described, and R⁴ represents a straight-chain or branchedalkyl group having 1-5 carbon atoms or an aryl group having 6-12 carbonatoms) is obtained by mixing a 6-keto compound represented the generalformula (VIla) (wherein R¹, R², R³, R⁶, R⁷ and R⁸ are the same aspreviously defined) and a primary amine represented by the generalformula (VIII) (wherein R⁴ is the same as previously defined) in asolvent and hydrogenating in the presence of suitable amounts of acidand metal catalyst, or reducing with a metal hydride reducing agent inthe presence of acid. The hydrogenation reaction is more preferable inorder to obtain the α-amino isomer with high selectivity. However,although the ratio varies according to the substrate, in the case ofreduction using a metal hydride reducing agent, both the α form and βisomer are obtained simultaneously. Thus, this method is preferable inthat it makes it possible to obtain a compound having the desiredstereochemistry by using ordinary separation and purificationtechniques. In addition, the method in which the amine is obtained isalso useful in the case of substrates having functional groups, such asolefins and so on, that react under hydrogenation conditions.

In the case of reduction using a hydrogenation reaction, 1-30equivalents, and preferably 1-10 equivalents, of amine are used.Although any solvent including alcohols such as methanol and ethanol,ethers such as THF, ether, DME and dioxane, or aromatic hydrocarbonssuch as benzene and toluene, can be used as a reaction solvent as longas it is inert under hydrogenation conditions, alcohols are preferablyused, with methanol used particularly preferably. Although any acidincluding inorganic acids such as hydrochloric acid, hydrobromic acid,sulfuric acid and phosphoric acid, or organic acids such as sulfonicacids including methanesulfonic acid and p-toluenesulfonic acid, benzoicacid, acetic acid or oxalic acid, can be used as long as it forms a saltwith an amine, hydrochloric acid, sulfuric acid and methanesulfonic acidare preferably used. Normally, the use of hydrochloric acid in an amountof 1 equivalent less than the total amount of base yields satisfactoryresults. These acids can also be added to a reaction system afterconverting the substrate and reaction agents into salts in advance.Although all catalysts, including platinum catalysts such as platinumoxide and platinum hydroxide, palladium catalysts such as palladiumhydroxide and palladium-carbon, and nickel catalysts such as Raneynickel, that are normally used in hydrogenation reactions can be used asa metal catalyst, platinum catalysts, and particularly platinum oxide,are used preferably. The reaction temperature is −30° C. to 80° C., andpreferably −10° C. to 50° C., and the hydrogen pressure is 1-100atmospheres and preferably 1-30 atmospheres. However, carrying out thereaction at room temperature and atmospheric pressure normally yieldspreferable results.

When reducing with a metal hydride, 1-30 equivalents, and preferably1-15 equivalents, of amine are used. Although alcohols solvents such asmethanol and ethanol, ethers such as THF, ether, DME and dioxane, oraromatic hydrocarbons such as benzene and toluene, can be used for as asolvent, alcohols are used preferably, with methanol used particularlypreferably. Although any acid, including inorganic acids such ashydrochloric acid, hydrobromic acid, sulfuric acid and phosphoric acid,and organic acids such as sulfonic acids including methanesulfonic acid,p-toluenesulfonic acid, benzoic acid, acetic acid and oxalic acid, maybe used in the reaction provided that it normally forms a salt withamines, hydrochloric acid, sulfuric acid and methanesulfonic acid arepreferably used. In addition, these acids may also be added to thereaction system after converting the substrate and reaction agents intosalts in advance. The metal hydride reducing agent used is that whichallows the reaction to be carried out relatively stably in the presenceof acid, examples of which include sodium borohydride, sodiumcyanoborohydride, zinc borohydride, sodium triacetoxyborohydride,tetramethylammonium triacetoxyborohydride and boranepyridine, withsodium cyanoborohydride used particularly preferably. Although thereaction can be carried out at a reaction temperature of −30° C. to 100°C. and preferably −10° C. to 50° C., satisfactory results can normallybe obtained at room temperature.

As shown in Chart 3, a 6β-amino compound represented by the generalformula (IIaβ2) (wherein R¹, R², R³, R⁶, R⁷ and R⁸ are the same aspreviously defined, and R⁴ represents a straight-chain or branched alkylgroup having 1-5 carbon atoms or an aryl group having 6-12 carbon atoms)can be obtained from a 6-keto compound represented by the generalformula (VIIb) (wherein R¹, R², R³, R⁶, R⁷ and R⁸ are the same aspreviously defined) with the 3 steps described below.

Step 1 involves the obtaining of an iminium intermediate represented bythe general formula (X) (wherein R¹, R², R³, R⁴, R⁶, R⁷ and R⁸ are thesame as previously defined) by reaction of a keto compound with asecondary amine compound having at least one benzyl substituent grouprepresented by the general formula (IX) (wherein R⁴ is the same asdefined above) in the presence of acid. It is desirable that thereaction be carried out while removing water produced either byazeotropic distillation or in the presence of a dehydrating agent. 1-30equivalents, and preferably 1-10 equivalents, of secondary amine areused. Although any acid, including inorganic acids such as hydrochloricacid, hydrobromic acid, sulfuric acid and phosphoric acid, or organicacids such as sulfonic acids including methanesulfonic acid andp-toluenesulfonic acid, benzoic acid, acetic acid and oxalic acid, canbe used in the reaction as long as it forms a salt with amine,hydrochloric acid, sulfuric acid, methanesulfonic acid and benzoic acidare used preferably, with hydrochloric acid and benzoic acid usedparticularly preferably. A method wherein these acids are added to thesystem after converting the substrate and reaction agents into salts inadvance is also preferably carried out.

Moreover, in the case of carrying out the reaction in the presence of aweak acid, there are cases wherein preferable results are obtained if astrong acid such as inorganic acids such as hydrochloric acid,hydrobromic acid, sulfuric acid and phosphoric acid, or sulfonic acidssuch as methanesulfonic acid, p-toluenesulfonic acid andcampher-sulfonic acid especially a strong acid such as p-toluenesulfonicacid is added as an acid catalyst. Examples of reaction solvents thatcan be used include ethers such as THF, ether, DME and dioxane,halocarbons such as dichloromethane and chloroform, aromatichydrocarbons such as benzene, toluene and xylene, esters such as ethylacetate and methyl acetate, or mixtures thereof. When using aconventional Dean-Stark water separator for the purpose of removingwater, solvents are used preferably that have excellent azeotropicefficiency and water separation efficiency, such as aromatichydrocarbons such as benzene and toluene. In this case, the mixing of asolvent such as ethyl acetate, THF or the like, for the purpose oflowering the azeotropic temperature, in amounts that do not lower waterseparation efficiency may provide preferable results. Although atemperature of 40-200° C., and preferably 50-150° C., can be consideredas a reaction temperature, satisfactory results can be obtained at areaction temperature of 50-130° C. In addition, it has also been foundthat a new method is effective wherein a dehydrating agent is packedinto a Soxhlet type extractor followed by continuous removal of water.Although any of the solvents mentioned above can be used as a solvent inthis case, ethers, esters and aromatic hydrocarbons, and particularlyTHF, DME, ethyl acetate, benzene and toluene, are preferably used.Although examples of dehydrating agents include molecular sieves andinorganic dehydrating agents such as anhydrous calcium sulfate,anhydrous copper sulfate, anhydrous sodium sulfate, anhydrous magnesiumsulfate and calcium chloride, molecular sieves are used particularlypreferably. The amount used is 1-100 times, and preferably 1-30 times ascalculated from their water retentivity and the amount of moisturetheoretically produced. Although a temperature of 40-200° C., andpreferably 50-150° C., can be considered as a reaction temperature,satisfactory results are obtained at a reaction temperature of 50-120°C. In addition, a method can also be carried out wherein the reaction isallowed to proceed by directly adding dehydrating agent to the reactionsystem. Examples of dehydrating agents include molecular sieves,inorganic dehydrating agents such as anhydrous calcium sulfate,anhydrous copper sulfate, anhydrous sodium sulfate, anhydrous magnesiumsulfate and calcium chloride, or titanium compounds having dehydrationability such as tetraisopropoxytitanium and titanium tetrachloride. Inthis case also, an amount used is 1-100 times, and preferably 1-30 timesas calculated from the water retentivity and the amount of moisturetheoretically produced. Although a temperature of −80-100° C. can beconsidered as a reaction temperature, satisfactory results are obtainedat a reaction temperature of −30-50° C.

Step 2 is a step involving conversion to a 6-N-alkyl-N-benzylaminocompound represented by the general formula (XI) (wherein R¹, R², R³,R⁴, R⁶, R⁷ and R⁸ are the same as previously defined) by reducing withmetal hydride reducing agent without isolating iminium salt. Althoughthe same solvent used in step 1 may be used as is for the reactionsolvent of this step, preferable results are obtained by reacting aftermixing an alcohols such as methanol or ethanol, and particularlymethanol. Naturally, the reaction may also be carried out with onlyalcohols such as methanol or ethanol after distilling off the reactionsolvent of step 1 under reduced pressure. The reaction can be carriedout with metal hydride reducing agent that is relatively stable underconditions in the presence of acid, such as sodium borohydride, sodiumcyanoborohydride, zinc borohydride, sodium triacetoxyborohydride,tetramethylammonium triacetoxyborohydride and boranepyridine,particularly preferably sodium cyanoborohydride. The reaction is carriedout a reaction temperature of −20-150° C., and preferably 0-120° C. Theresulting 6-N-alkyl-N-benzylamino compound represented by the generalformula (XI) (wherein R¹, R², R³, R⁴, R⁶, R⁷ and R⁸ are the same aspreviously defined) can also be obtained using a secondary amine byperforming reductive amination using the metal hydride reducing agentsof Chart 2. Moreover, if this step is performed using a correspondingsecondary amine, the compound of general formula (I) can be obtainedwherein A is —NR⁴—.

Step 3 involves removing a benzyl group under reducing conditions toform a 6β-amino form (IIaβ2). In this step, reacting the substrateeither after converting into a salt in advance using an inorganic acidsuch as hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoricacid, or an organic acid such as sulfonic acids includingmethanesulfonic acid, p-toluenesulfonic acid or camphersulfonic acid,benzoic acid, acetic acid, oxalic acid or phthalic acid, and preferablyhydrochloric acid or phthalic acid, or adding suitable amount of theseacids prior to the reaction, yields favorable results. Since there arecases in which a resulting secondary amine salt can be purified as acrystal depending on the acid, selection of acid is important. Forexample, when phthalic acid is used with a compound wherein R¹ is acyclopropylmethyl group, R² and R³ are hydroxy groups, R⁴ is a methylgroup, R⁶ and R⁷ are together —O— and R⁸ is a hydrogen atom, acrystalline salt is obtained that is easily purified. Although anysolvent such as alcohol-based solvents such as methanol and ethanol,ethers such as THF, ether, DME and dioxane, and organic hydrocarbonssuch as benzene and toluene, can be used as a reaction solvent providedit is inert under hydrogenation conditions, alcohols are usedpreferably, with methanol used particularly preferably. Although anycatalyst that is used in normal hydrogenation reactions, such as,platinum catalysts such as platinum oxide and platinum hydroxide,palladium catalysts such as palladium hydroxide and palladium-carbon,and nickel catalysts such as Raney nickel, can be used as a metalcatalyst, palladium catalysts, and particularly palladium-carbon, areparticularly preferably used. The reaction temperature is −30 to 80° C.,and preferably −10 to 50° C. while hydrogen pressure is 1 to 100atmospheres, and preferably 1 to 30 atmospheres. However, carrying outthe reaction at room temperature and atmospheric pressure normallyyields favorable results.

In addition, when ammonium acetate is used in place of primary amine inthe reductive amination reaction shown in Chart 2, when dibenzylamine isused in the method shown in Chart 3, or after converting ketone intooxime using the method described in the literature (J. Med. Chem., 27,1727 (1984)), a primary amine can be obtained by reducing with borane orunder hydrogenation conditions. This primary amine can be converted intoa secondary amine by effecting the acylation and reduction of step 2.This is also useful as an alternative route for obtaining the secondaryamine.

As shown in Chart 4, a 6-α-alcohol represented by the general formula(IIbα) (wherein R¹, R², R³, R⁶, R⁷ and R⁸ are the same as previouslydefined) is obtained either by reducing with metal hydride reducingagent or hydrogenation in the presence of acid and metal catalyst.Although metal hydride reducing agents including sodium borohydride,sodium cyanoborohydride, zinc borohydride, sodium triacetoxyborohydride,L-selectride and lithium aluminum hydride can be used, sufficientlysatisfactory results are obtained with sodium borohydride. Althoughsolvents including alcohols such as methanol and ethanol, and etherssuch as THF, ether, DME and dioxane are used, alcohols, and particularlymethanol, are preferably used. In the case of hydrogenation, examples ofsolvents that are used include alcohols such as methanol and ethanol,and ethers such as THF, ether and dioxane, with alcohols being usedpreferably, and methanol being used particularly preferably.

Although acids such as inorganic acids such as hydrochloric acid,hydrobromic acid, sulfuric acid or phosphoric acid, and organic acidssuch as sulfonic acids including methanesulfonic acid andp-toluenesulfonic acid, benzoic acid are used, acetic acid or oxalicacid, hydrochloric acid is preferably used. Although all catalysts thatare used in normal hydrogenation reactions such as platinum catalystssuch as platinum oxide or platinum hydroxide, palladium catalysts suchas palladium hydroxide or palladium-carbon, and nickel catalysts such asRaney nickel can be used as a metal catalyst, platinum catalysts, andparticularly platinum oxide are preferably used. Although the reactioncan be carried out at a reaction temperature of −30-80° C., andpreferably −10-50° C., and under a hydrogen pressure of 1-100atmospheres, and preferably 1-30 atmospheres, favorable results arenormally obtained at room temperature and under atmospheric pressure.

As shown in Chart 5, a 6β-hydroxy form represented by the generalformula (IIbβ) (wherein R¹, R², R³, R⁶, R⁷ and R⁸ are the same aspreviously defined) can be obtained by reacting a 6-keto formrepresented by the general formula (Vila) (wherein R¹, R², R³, R⁶, R⁷and R⁸ are the same as previously defined) with formamidine sulfinicacid in the presence of a base. Preferable examples of a base usedinclude inorganic bases such as sodium hydroxide, potassium hydroxide,potassium carbonate and sodium bicarbonate, with sodium hydroxide beingused particularly preferably. Although examples of reaction solventsused include water, alcohols such as methanol and ethanol, and aprotic,dipolar solvents such as DMF and DMSO, the use of water normally yieldssatisfactory results. Although a temperature of 0-150° C. is consideredas a reaction temperature, a temperature of 60-100° C. is preferable.

Among the 6-amino or 6-hydroxy compound synthesized in the above method,particularly a compound wherein R³ is a hydrogen atom, is obtained bymethods similar to those shown in Charts 2, 3, 4 and 5, using as astarting material a 3-dehydroxy-6-keto compound represented by thegeneral formula (VIIe) (wherein R¹, R², R⁶, R⁷ and R⁸ are the same aspreviously defined, provided that R⁷ is not a hydroxy group), obtainedby using as a substrate a 3-hydroxy-6-keto compound represented by thegeneral formula (VIIc) (wherein R¹, R², R⁶, R⁷ and R⁸ are the same aspreviously defined, provided that R⁷ is not a hydroxy group) accordingto the scheme shown in Chart 6. In addition, an intermediate, wherein R³is a siloxy group, can be obtained by methods similar to those shown inCharts 2, 3, 4 and 5, by using for as a starting material a3-siloxy-6-keto form represented by the general formula (VIIf) (whereinR¹, R², R⁶, R⁷ and R⁸ are the same as previously defined, provided thatR⁷ is not a hydroxy group and G represents an alkylsilyl group),obtained from a 3-hydroxy-6-keto compound (VIIc) by the scheme shown inChart 7.

Namely, as shown in Chart 6, the first step for obtaining a3-dehydroxy-6-keto compound represented by the general formula (VIIe)(wherein R¹, R², R⁶, R⁷ and R⁸ are the same as previously defined,provided that R⁷ is not a hydroxy group) is a step whereintrifluoromethane sulfonic anhydride is caused to act on a phenolichydroxyl group in the presence of a base to form a trifrate formrepresented by the general formula (VIId) (wherein R¹, R², R⁶, R⁷ and R⁸are the same as previously defined, provided that R⁷ is not a hydroxygroup). Although solvents such as halocarbons such as dichloromethaneand chloroform, ethers such as THF, ether, DME and dioxane, and amineshaving large steric hindrances that can be used as solvents such as2,6-lutidine and diisopropylethylamine, can be considered for use as areaction solvent, halocarbons, and particularly dichloromethane, arepreferably used.

Although tertiary amines such as triethylamine, diisopropylethyl amineand proton sponge, as well as pyridine, 2,6-lutidine and imidazole areused as a coexisting base, 2,6-lutidine is preferably used. Although thereaction can be carried out at −30-50° C., satisfactory results can benormally attained at a temperature of 0° C. to room temperature normallyyields. Step 2 is a step wherein a trifrate form is reduced with formicacid in the presence of phosphorous ligand and a base using a palladiumcatalyst. Although amines usable as solvents such as triethylamine anddiisopropylethylamine, ethers such as THF, ether, DME and dioxane,aromatic hydrocarbons such as benzene and toluene, and aprotic dipolarsolvents such as DMF and DMSO are used for the reaction solvent, DMF isparticularly preferably used. Although zero-valent complexes such astetrakuistriphenylphosphine palladium and bisbenzylideneacetonepalladium, and bivalent complexes such as palladium acetate andpalladium chloride are frequently used for the palladium catalyst,palladium acetate is used normally.

Although monodentate phosphines such as trimethylphosphine,triethylphosphine, triphenylphosphine and tris-o-toluphosphine, andbidentate phosphines such as bis-(diphenylphosphino)methane,1,2-bis-(diphenylphosphino) ethane, 1,3-bis-(diphenylphosphino)propaneand 1,1′-bis-diphenylphosphinoferrocene, are used as a phosphorousligand, 1,1′-bis-diphenylphosphinoferrocene is particularly preferablyused. Although amines such as triethylamine and diisopropylethylamine,and inorganic salts such as silver carbonate, sodium acetate andpotassium acetate, are used as a base used in the reaction,triethylamine is preferably used. The reaction is carried out at areaction temperature of 0-150° C., and satisfactory results are normallyobtained at a room temperature to 80° C.

As shown in Chart 7, a 3-hydroxy-6-keto form represented by the generalformula (VIIc) (wherein R¹, R², R⁶, R⁷ and R⁸ are the same as previouslydefined) may be reacted with silylchloride in the presence of a base toobtain a 3-siloxy-6-keto form represented by the general formula (VIIf)(wherein R¹, R², R⁶, R⁷ and R⁸ are the same as previously defined,provided that R⁷ is not a hydroxy group and G represents an allcylsilylgroup). Although trimethylsilylchloride, triphenylsilylchloride,t-butyldimethylsilylchloride and diphenylmethylsilylchloride arementioned as silylchlorides, t-butyldimethylsilylchloride is preferablyused. Although tertiary amines such as triethylamine,diisopropylethylamine and proton sponges, as well as pyridine,dimethylaminopyridine and imidazole are used as a base, imidazole ispreferably used. Although halocarbons such as dichloromethane,chloroform, carbon tetrachloride and 1,2-dichloroethane, ethers, such asether, THF, DME and dioxane, and pyridine are used as a solvent,dichloromethane is preferably used. The reaction can be carried outwithin a range of −80-100° C., and preferable results are obtainedparticularly in the vicinity of 0° C. to room temperature. Although thereaction can be carried out in 5-300 minutes, since there are cases inwhich 6th position ketone groups are also enolsilylated when reactiontime is lengthened particularly with respect to compounds wherein is asingle bond and R⁶ and R⁷ together are —O—, a reaction time of 5-60minutes is preferable.

As shown in Chart 8, compounds wherein X is NR⁴ can be obtained bycondensing a 6-amino form represented by the general formula (IIa)(wherein R¹, R², R³, R⁶, R⁷ and R⁸ are the same as previously defined,and R⁴ represents a straight-chain or branched alkyl group having 1-5carbon atoms or an aryl group having 6-12 carbon atoms), obtained by themethods shown in Charts 2 and 3, with a carboxylic acid and carboxylicacid derivative represented by the general formula (III) (wherein B andR⁵ are the same as previously defined), or with a formic acid derivativerepresented by the general formula (IV) (wherein Z, B and R⁵ are thesame as previously defined), or with a isocyanic acid or isothiocyanicacid derivative represented by the general formula (V) (wherein B and R⁵are the same as previously defined), or with a sulfonic acid derivativerepresented by the general formula (VI) (wherein B and R⁵ are the sameas previously defined), etc.

Condensation with a carboxylic acid derivative can be performed byreacting a 6-amino form with an acid chloride or acid anhydride thatreacts in the presence of a base, or by reacting with carboxylic aciditself using, for example, N,N′-dicyclohexylcarbodiimide (abbreviated asDCC), 1,1′-carbonyldiimidazole, or bis-(2-oxo-3-oxazolidinyl)phosphinatechloride (abbreviated as BOPC), etc. Acid chloride or acid anhydride isused in an amount of 1-20 equivalents, and preferably 1-5 equivalents.Although halocarbons such as dichloromethane, chloroform, carbontetrachloride and 1,2-dichloroethane, ethers such as ether, THF, DME anddioxane, pyridine, water or a mixture of these are used as reactionsolvents, when using acid chloride, chloroform or a mixed solvent of THFand water is used preferably. In the case of using acid anhydride,pyridine is preferably used both as base and solvent. Although organicbases such as tertiary amines including triethylamine,diisopropylethylamine and proton sponges, pyridine,dimethylaminopyridine and imidazole, and inorganic bases such aspotassium carbonate, sodium carbonate, sodium bicarbonate, sodiumhydroxide and potassium hydroxide are used as bases, when usingchloroform as the solvent, trimethylamine is normally used in an amountof 1-20 equivalents, and preferably 1-5 equivalents. In the case ofusing a mixed solvent of THF and water, the use of potassium carbonate,sodium carbonate or sodium bicarbonate in an amount of 1-20 equivalents,and preferably 1-5 equivalents, provides satisfactory results. Thereaction can be carried out within a range of −80-100° C., andpreferable results are obtained particularly at a temperature of from 0°C. to room temperature. In the case of using DCC as a condensing agent,an amount of 1-20 equivalents preferably 1-5 equivalents is used.Although halocarbons such as dichloromethane, chloroform, carbontetrachloride and 1,2-dichloroethane, and ethers such as ether, THF, DMEand dioxane are used as reaction solvents, dichloromethane andchloroform are particularly preferably used. Although organic bases suchas tertiary amines including triethylamine, diisopropylethylamine andproton sponges, as well as pyridine, dimethylaminopyridine and imidazoleare used as coexisting bases, dimethylaminopyridine in an amount of0.01-2 equivalents is used particularly preferably. The reaction can becarried out within a range of −80-100° C., and preferable results areobtained in the vicinity of 0° C. to room temperature in particular.

In the case of using 1,1′-carbonyldiimidazole as a condensing agent, anamount of 1-20 equivalents, and preferably 1-5 equivalents is used.Although ethers such as ether, THF, DME and dioxane, and halocarbonssuch as dichloromethane, chloroform, carbon tetrachloride and1,2-dichloroethane are used as reaction solvents, THF is particularlypreferably used. The reaction can be carried out within a range of−20-120° C., and a temperature in the vicinity of room temperature to100° C. is particularly preferable. In the case of using BOPC1 as acondensing agent, it is used in an amount of 1-20 equivalents, andpreferably 1-5 equivalents. Examples of solvents used for the reaction(solvent) include halocarbons such as dichloromethane, chloroform,carbon tetrachloride and 1,2-dichloroethane, and ethers such as ether,THF, DME and dioxane, though dichloromethane and chloroform areparticularly preferably used. Although organic bases such as tertiaryamines including triethylamine, diisopropylethylamine, proton sponge andN-ethylpiperidine, as well as pyridine, dimethylaminopyridine andimidazole are used as coexisting bases, N-ethylpiperidine in an amountof 1-20 equivalents, and preferably 1-5 equivalents, is particularlypreferably used. The reaction can be carried out within a range of−80-100° C., and preferable results are obtained at 0-50° C. inparticular.

Condensation with a formic acid derivative can be performed by reactinga 6-amino form with 1-20 equivalents and preferably 1-5 equivalents ofan acid chloride that reacts in the presence of base. Althoughhalocarbons such as dichloromethane, chloroform, carbon tetrachlorideand 1,2-dichloroethane, ethers such as ether, THF, DME and dioxane,water or mixtures of these solvents are used as reaction solvents,chloroform and a mixed solvent of THF and water are particularlypreferably used. Although organic bases such as tertiary aminesincluding triethylamine, diisopropylethylamine and proton sponge,pyridine, dimethylaminopyridine and imidazole, and inorganic bases suchas potassium carbonate, sodium carbonate and sodium bicarbonate are usedas bases, triethylamine in an amount of 1-20 equivalents, and preferably1-5 equivalents provides satisfactory results when chloroform is used asa solvent, while potassium carbonate, sodium carbonate and sodiumbicarbonate used in an amount of 1-20 equivalents, and preferably 1-5equivalents, normally provides favorable results when a mixed solvent ofTHF and water is used as a solvent. The reaction can be carried outwithin a range of −80-100° C., and preferable results are obtained from0° C. to the vicinity of room temperature.

Condensation with an isocyanic acid or isothiocyanic acid derivative canbe performed by reacting 1-20 equivalents, and preferably 1-5equivalents, of a corresponding isocyanate ester with a 6-amino form.Although halocarbons such as dichloromethane, chloroform, carbontetrachloride and 1,2-dichloroethane, and ethers such as ether, THF, DMEand dioxane are used as reaction solvents, chloroform is particularlypreferably used. The reaction can be carried out within a range of−80-100° C., and preferable results are obtained from 0° C. to thevicinity of room temperature.

Condensation with a sulfonic acid derivative can be performed byreacting 1-20 equivalents, and preferably 1-5 equivalents, of thecorresponding sulfonate chloride with a 6-amino form in the presence ofbase. Examples of bases that are used include tertiary amines such astriethylamine, diisopropylethylamine and proton sponges, as well aspyridine, dimethylaminopyridine and imidazole. Although halocarbons suchas dichloromethane, chloroform, carbon tetrachloride and1,2-dichloroethane, ethers such as ether, THF, DME and dioxane, andpyridine are used as bases, pyridine is particularly preferably used asboth base and solvent. The reaction can be carried out within a range of−80-100° C., and preferable results are obtained from 0° C. to thevicinity of room temperature in particular.

In the case of compounds wherein R³ is a hydroxy group in particular,since there are cases in which phenolic hydroxyl groups may reactsimultaneously, after carrying out step 1 in the same manner as shown inChart 8, as shown in Charts 9-11 with carboxylic acid derivative, formicacid derivative and isocyanic acid or isothiocyanic acid derivative, thetarget compound can be obtained by performing alkaline treatment forstep 2. Examples of solvents used for a reaction solvent of step 2include water, alcohols such as methanol and ethanol, ethers such asether, THF, DME and dioxane, or mixed solvents of those solvents. Whensolubility is inadequate, halocarbons such as dichloromethane andchloroform can be suitably added. Examples of bases used includeinorganic bases such as potassium carbonate, sodium carbonate, sodiumbicarbonate, sodium hydroxide and potassium hydroxide. Normally, 1-20equivalents, and preferably 1-10 equivalents, of potassium carbonate,sodium hydroxide and so forth are used preferably. The reaction can becarried out within a range of −80-100° C., and favorable results areobtained from 0-50° C. in particular.

When condensing compounds wherein R³ is a hydroxy group with suif onicacid derivative, as shown in Chart 12, preferable results are obtainedby using a 3-siloxy-6-amino form, wherein phenolic hydroxyl groups areprotected in advance with silylether groups and so forth, represented bythe general formula (IIc) (wherein R1, R2, R4, R6, R7, R8 and G are thesame as previously defined). Naturally, the following method can also beapplied to condensation with a carboxylic acid derivative, formic acidderivative and isocyanic acid or isothiocyanic acid derivative. Namely,this method involves removing silyl groups after carrying out step 1 inthe same manner as shown in Chart 8. Although quaternary ammonium saltssuch as tetrabutylammonium fluoride, tetrabutylammonium chloride andpyridinium hydrofluoride, or acids such as acetic acid, hydrochloricacid, sulfuric acid and hydrofluoric acid, are used for removal of silylgroups in step 2, normally 1-20 equivalents, and preferably 1-5equivalents, of tetrabutylammonium fluoride are used. Although etherssuch as THF, ether, DME and dioxane, halocarbons such as dichloromethaneand chloroform, and acetonitrile are used as solvents, THF isparticularly preferably used. Although the reaction can be carried outat −20-100° C., satisfactory results can normally be obtained at roomtemperature.

In addition, a 6-amino form represented by the general formula (Im)(wherein R¹, R², R³, R⁴, B, R⁵, R⁶, R⁷ and R⁸ are the same as previouslydefined), in which A is —NE⁴—, is obtained by reducing an amide formrepresented by the general formula (Ie′) (wherein R¹, R², R³, R⁴, R⁵,R⁶, R⁷, R⁸ and B are the same as previously defined) using a metalhydride reducing agent. Examples of reducing agents used include metalhydride compounds having a strong reducing activity such as lithiumaluminum hydride, aluminum diisobutylaluminurrhydride, aluminum hydride,lithium borohydride and diborane, 1-20 equivalents, and preferably 1-5equivalents of diborane are particularly preferably used. Ethers such asTHF, DME, ether and dioxane are used preferably as a solvent when usinglithium aluminum hydride, lithium borohydride or diborane, with THFbeing used particularly preferably. Aromatic hydrocarbons such asbenzene and toluene are used preferably as a solvent whendiisobutylaluminumhydride or aluminum hydride are used. The reaction canbe carried out within a range of −40 to 100° C. and a temperature from0° C. to the vicinity of room temperature is preferable.

As shown in Chart 14, compounds wherein X is O can be obtained bycondensing a 6-hydroxy form represented by the general formula (IIb)(wherein R¹, R², R³, R⁶, R⁷ and R⁸ are the same as previously defined)obtained in Charts 4 and 5, with a carboxylic acid derivative (III), aformic acid derivative (IV), an isocyanic acid, an isothiocyanic acidderivative (V), or sulfonic acid derivative (VI) and so forth.

Condensation with a carboxylic acid derivative can be performed bytreatment of a 6-hydroxy compound with 1-20 equivalents, and preferably1-5 equivalents of an acid chloride or acid anhydride in the presence ofbase. Although halocarbons such as dichloromethane, chloroform, carbontetrachloride and 1,2-dichloroethane, ethers such as ether, THF, DME anddioxane, and pyridine are used as a reaction solvents, chloroform isused preferably when using acid chloride, while pyridine is usedpreferably in the case of using acid anhydride. Although tertiary aminessuch as triethylamine, diisopropylethylamine and proton sponge, as wellas pyridine, dimethylaminopyridine and imidazole are used as bases, theuse of both diisopropylethylamine and dimethylaminopyridine in an amountof 1-20 equivalents, and preferably 1-5 equivalents, normally providessatisfactory results. The reaction can be carried out at −80 to 100° C.,and preferable results are obtained at a temperature of from thevicinity of room temperature to 80° C. in particular.

Condensation with a formic acid derivative can be performed by reactinga 6-hydroxy form with 1-20 equivalents, and preferably 1-5 equivalents,of an acid chloride that reacts in the presence of a base. Althoughhalocarbons such as dichloromethane, chloroform, carbon tetrachlorideand 1,2-dichloroethane, and ethers such as ether, THF, DME and dioxaneare used as reaction solvents, chloroform and carbon tetrachloride areused particularly preferably. Although tertiary amines such astriethylamine, diisopropylethylamine and proton sponges, as well aspyridine, dimethylaminopyridine and imidazole are used as bases, the useof both diisopropylethylamine and dimethylaminopyridine in an amount of1-20 equivalents, and preferably 1-5 equivalents, normally providessatisfactory results. The reaction can be carried out within a range of−80 to 100° C., and preferable results are obtained from the vicinity ofroom temperature to 80° C. in particular.

Condensation with an isocyanic acid or isothiocyanic acid derivative canbe performed by reacting 1-20 equivalents, and preferably 1-5equivalents, of the corresponding isocyanate ester with a 6-hydroxyform. Although halocarbons such as dichloromethane, chloroform, carbontetrachloride and 1,2-dichloroethane, and ethers such as ether, THF, DMEand dioxane are used as reaction solvent, chloroform is usedparticularly preferably. The reaction can be carried out within a rangeof −80 to 100° C., and preferable results are obtained at a temperatureof from the vicinity of room temperature to 80° C. in particular.

Condensation with a sulfonic acid derivative can be carried out bytreatment of 1-20 equivalents, and preferably 1-5 equivalents, of acorresponding sulfonic chloride with a 6-hydroxy form in the presence ofa base. Examples of a base used include tertiary amines such astriethylamine, diisopropylethylamine and proton sponges, as well aspyridine, dimethylaminopyridine and imidazole. Although halocarbons suchas dichloromethane, chloroform, carbon tetrachloride and1,2-dichloroethane, ethers such as THF, DME and dioxane, and pyridineare used as reaction solvent, pyridine is used particularly preferably,both as base and solvent. The reaction can be carried out within a rangeof −80 to 100° C., and preferable results are obtained at a temperatureof the vicinity of room temperature to 80° C. in particular.

In the case of compounds wherein R³ is a hydroxy group in particular,since phenolic hydroxyl group also reacts simultaneously, in the case ofcarboxylic acid derivative, formic acid derivative, and isocyanic acidor isothiocyanic acid derivative, after performing a condensationreaction in the same manner as shown in Chart 14 as step 1, the targetcompound can be obtained by performing alkaline treatment for step 2 asshown in Charts 15-17. Examples of solvents used as reaction solvent ofstep 2 include alcohols such as methanol and ethanol, and whensolubility is not adequate, halocarbons such as dichloromethane, andchloroform can ben suitably added. Examples of a base used includeinorganic bases such as potassium carbonate, sodium carbonate, sodiumbicarbonate, sodium hydroxide and potassium hydroxide, with potassiumcarbonate normally being used preferably. The reaction can be carriedout within a range of −80 to 100° C., and preferable results areobtained at −20 to 50° C. in particular. However, since solvolysis offunctional group at the 6 position may also proceed, in such cases, thisproblem is solved by either lowering the reaction temperature orshortening the reaction time.

The use of a 3-siloxy-6-hydroxy form represented by the general formula(IId) (wherein R¹, R², R⁶, R⁷, R⁸ and G are the same as previouslydefined), in which phenolic hydroxyl groups are protected in advancewith silylether group and so forth, for condensation with a sulfonicacid derivative yields preferable results. Naturally, this method can becarried out for condensation with a carboxylic acid derivative, a formicacid derivative, an isocyanic acid or an isothiocyanic acid derivative.After performing condensation in the same manner as shown in Chart 14 asstep 1, silyl group is removed in step 2. Although quaternary ammoniumsalts such as tetrabutylammonium fluoride, tetrabutylammonium chlorideand pyridinium hydrofluoride, or acids such as acetic acid, hydrochloricacid, sulfuric acid and hydrofluoric acid, may be used for removal ofsilyl groups, normally 1-20 equivalents, and preferably 1-5 equivalents,of tetrabutylammonium fluoride are used. Examples of solvents usedinclude ethers such as THF, DME and dioxane, acetonitrile andhalocarbons such as dichloromethane and chloroform, though THF is usedparticularly preferably. Although the reaction can be carried out at−20-100° C., satisfactory results are normally obtained at roomtemperature.

The free base obtained in the above steps can be converted into thesalts with pharmacologically acceptable acids specifically by themethods shown below. Namely, a resulting free base is dissolved orsuspended in a solvent followed by addition of acid and filtering of theprecipitated solid or crystal, or in the case of not precipitating, asolvent of lower polarity is added, or the solvent is substituted with asolvent of lower polarity and filtering after precipitation.Alternatively, concentration and drying are performed after forming asalt. However, in the case organic solvent remains in these methods,drying under reduced pressure may be performed after freeze-drying in anaqueous solution. Examples of solvents used to dissolve or suspend theabove free base include water, alcohols such as methanol, ethanol andisopropyl alcohol, halocarbons such as dichloromethane and chloroform,ethers such as ether, THF, DME and dioxane, esters such as ethyl acetateand methyl acetate, or their mixed solvents, while preferable examplesinclude methanol, ethanol, isopropyl alcohol, ethyl acetate, chloroform,chloroform-methanol, water-methanol, and water-ethanol. Preferableexamples of solvents used for precipitating solid include ether andethyl acetate. Although it is desirable that an equivalent amount ofacid be added, when it is possible to remove excess acid after washingthe resulting salt, 1-10 equivalents may be used. In addition, acid maybe added as is or suitably dissolved in the above-mentioned solvents andthen added. For example, hydrochloric acid can be added in the form ofconcentrated hydrochloric acid, 1 N aqueous solution, a saturatedmethanol solution or a saturated ethyl acetate solution, while tartaricacid can be added in the form of a solid, an aqueous solution or amethanol solution. At the time of salt formation, since the temperatureof the system may rise due to the heat of neutralization, there arecases in which favorable results are obtained if a water bath or icebath is used.

As a result of in vitro and in vivo pharmacological testing, thecompounds of the present invention represented by the general formula(I) are known to have strong analgesic and diuretic activity as anopioid κ-agonist, and it became clear that it can be expected to be usedas a useful analgesic and diuretic. In addition, based on the propertiesof κ-agonists, it is also possible to use this compound as a hypotensiveand sedative. Moreover, it was also found that the compounds of thepresent invention also include agonists highly selective forδ-receptors, thus suggesting the possibility of their use as animmunoenhancer, anti-HIV agent and so forth.

At the time of clinical use of the analgesic or diuretic of the presentinvention, it may be used as in the form of a free base or its salt, orsuitably mixed with vehicles such as stabilizer, buffer, diluent,isotonic agents and preservatives. Examples of administration formsinclude injection preparations; oral preparations such as capsules,powders, granules and syrup, transintestinal administration in the formof suppositories; or topical administration in the form of ointments,creams and plasters. It is desirable that the analgesic of the presentinvention contain 1-90% by weight, and preferably 30-70% by weight ofthe above-mentioned active ingredient. Although the amount used issuitably selected according to symptoms, age, body weight andadministration method, the adult dose as the amount of active ingredientin the case of an injection preparation is 0.0001 mg-1 g per day, and0.005 mg-10 g per day in the case of an oral preparation. In both cases,administration may be performed in a single dose or divided amongseveral administrations.

EXAMPLES

Although the following provides an explanation of the present inventionin the form of the specific examples described below, the presentinvention is not limited to these examples.

Reference Example 1 N-Acetylbenzylamine

10 g of benzylamine was dissolved in 200 ml of methylene chloridefollowed by the addition of 26 ml of triethylamine and dropwise additionof 7.3 ml of acetyl chloride at 0° C. After stirring for 1 hour at roomtemperature, 2 ml of methanol was added to the reaction system at 0° C.followed by 120 ml of water and separation of the phases. The aqueouslayer was extracted with 100 ml of chloroform, and the resulting organiclayer was concentrated after drying with anhydrous sodium sulfate toobtain 8.55 g of the target compound (yield: 61%).

NMR (90 MHz, CDCl₃); δ 1.9 (3H, s), 4.3 (2H, d, J=4.8 Hz), 6.8 (1H, brs), 7.3 (5H, s). IR (liquid film method); υ 3296, 1649, 1543, 1499,1377, 1359, 1284, 1077, 1033 cm⁻¹.

Reference Example 2 N-Benzylethylamine

2.96 g of the N-acetylbenzylamine obtained in reference example 1 wasdissolved in 45 ml of anhydrous tetrahydrofuran followed by the additionof 1.73 g of lithium aluminum hydride at 0° C. After stirring for 2hours at room temperature, the reaction mixture was refluxed whileheating for 2 hours. After cooling the reaction mixture to 0° C., 22.8 gof sodium fluoride was added followed by dropwise addition of 91 ml of10% aqueous tetrahydrofuran and stirred for 1 hour at room temperature.The precipitate was removed using Celite and the filtrate wasconcentrated to obtain 2.5 g of the target compound in liquid form(yield: 93%).

NMR (90 MHz, CDCl₃); δ 1.10 (3H, t, J=7.3 Hz), 1.4 (1H, brs), 2.65 (2H,q, J=7.3 Hz), 3.75 (2H, s), 7.15-7.4 (5H, m).

Reference Example 33-tert-butyldimethylsilyloxy-17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6-oxomorphinan2

3.49 g of naltrexone hydrochloride was suspended in 10.5 ml ofN,N-dimethylfonnamde. After adding 3.46 g of imidazole, 3.48 g oftert-butyldimethylchlorosilane was added followed by stirring for 35minutes at room temperature. 30 ml of water and 50 ml of diethyl etherwere added to the reaction system followed by separation. The aqueouslayer was extracted twice with 30 ml of diethyl ether. The combinedextracts were dried over anhydrous sodium sulfate and concentrated. Theresulting residue was recrystallized from ethanol to obtain 3.2 g of thetarget compound (yield: 76%).

NMR (90 MHz, CDCl₃); δ 0.0-1.2 (5H, m), 0.2 (3H, s), 0.3 (3H, s), 1.0(9H, s), 1.3-2.0 (3H, m), 2.0-3.2 (8H, m), 2.4 (2H, d, J=4.4 Hz), 4.60(1H, s), 6.5 (1H, d, J=6.4 Hz), 6.6 (1H, d, J=6.4 Hz).

Reference Example 4 3-Dehydroxynaltrexone 3

Naltrexone (5 g) was dissolved in dichloromethane (50 ml) followed bythe addition of 2,6-lutidine (2.56 ml) and anhydroustrifluoromethanesulfonic acid (2.96 ml) at 0° C. After reacting for 15minutes at the same temperature, distilled water (40 ml) and saturatedaqueous sodium bicarbonate (20 ml) were added followed by extractionwith chloroform (20+30 ml). After washing with saturated brine, theextracts was dried with anhydrous sodium sulfate and the solvent wasdistilled off. Ether (20 ml) was added and the precipitating solid wasfiltered out using Celite followed by initial purification with silicagel column chromatography (Merk 7734, 300 g; chloroform→1%methanol/chloroform).

The initially purified product was dissolved in anhydrous DMF (25 ml)and reacted with triethylamine (5.9 ml), palladium acetate (0.06 g),DPPF (0.16 g) and formic acid (1.1 ml) for 15 minutes at 60° C. Afterdistilling off the solvent, saturated aqueous sodium bicarbonate (20 ml)and distilled water (10 ml) were added followed by extraction withchloroform (30 ml×2). After washing with saturated brine and drying withanhydrous sodium sulfate, the solvent was distilled off and theresulting black oily substance was purified with silica gel columnchromatography (Merk 7734, 300 g; chloroform) to obtain the targetcompound (3.32 g, yield: 62%).

NMR (400 MHz, CDCl₃); δ 0.26 (2H, m), 0.57 (2H, m), 0.88 (1H, m), 1.54(1H, dd, J=12.7, 2.0 Hz), 1.63 (1H, dt, J=14.7, 3.9 Hz), 1.89 (1H, m),2.13 (1H, dt, J=12.7, 3.9 Hz), 2.31 (1H, dt, J=14.7, 2.9 Hz), 2.42 (3H,m), 2.63 (1H, dd, J=18.6, 5.7 Hz), 2.70 (1H, dd, J=12.7, 4.9 Hz), 3.04(1H, dt, J=14.7, 4.9 Hz), 3.11 (1H, d, J=19.5 Hz), 3.21 (1H, d, J=5.9Hz), 4.65 (1H, s), 5.0-5.5 (1H, br), 6.69 (1H, d, J=6.8 Hz), 6.75 (1H,d, J=6.8 Hz), 7.07 (1H, t, J=6.8 Hz); IR (neat); υ 3406, 1729, 1630,1607, 1458, 1052, 938, 781 cm⁻¹; Mass (EI); m/z 325 (M+).

Example 117-Cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan4

Naltrexone (1.0 g) and methylamine hydrochloride (0.99 g, 5 equivalents)were dissolved in methanol (15 ml) followed by stirring for 20 minutesat room temperature. This reaction solution was added to platinum oxide(0.05 g, 5 w %) in methanol (10 ml) activated in advance in a hydrogenatmosphere followed by hydrogenation for 4 hours at room temperature andatmospheric pressure. The catalyst was removed by Celite filtration andthe solvent was distilled off. After adding saturated aqueous sodiumbicarbonate (20 ml) and extracting with chloroform (20 ml×2), theextract was washed with saturated brine and dried with anhydrous sodiumsulfate, and the solvent was distilled off. The resulting darkreddish-violet oily substance was dissolved in chloroform (2 ml)followed by addition of ethyl acetate (4 ml) to obtain the targetcompound (0.83 g, yield: 79%) by crystallization. A portion of thiscompound was removed and various spectra were measured in the form of ahydrochloride. mp 270° C. (decomposition)

NMR (500 MHz, DMSO-d₆); δ 0.40 (1H, m), 0.48 (1H, m), 0.61 (1H, m), 0.69(1H, m), 0.95 (1H, m), 1.08 (1H, m), 1.47 (1H, m), 1.70 (1H, d, J=13.2Hz), 1.81 (1H, m), 1.92 (1H, m), 2.49 (1H, m), 2.68 (3H, s), 2.72 (1H,m), 3.00 (1H, m), 3.08 (2H, m), 3.26 (2H, m), 3.57 (1H, m), 4.01 (3H,m), 4.97 (1H, brs), 6.50 (1H, s), 6.65 (1H, d, J=8.3 Hz), 6.78 (1H, d,J=8.3 Hz), 9.20 (2H, m); 1R (KBr); υ 3200, 1510, 1464, 1238, 1116, 982,859 cm⁻¹. Mass (EI); m/z 356 (M+) (measured in the free form);Elementary Analysis: As C₂₁H₂₈N₂O₃.2HCl.0.2H₂O; Calculated values: C58.25; H 7.08; N 6.47; Cl 16.38; Measured values: C 58.35; H 7.20; N6.44; Cl 16.14.

Example 2

17-Cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-isobutylaminomorphinan5 was obtained by following the procedure of example 1 but usingisobutylamine instead of methylamine.

NMR (500 MHz, CDCl₃); δ 0.22 (2H, m), 0.53 (2H, m), 0.84 (1H, m), 0.92(1H, m), 0.94 (3H, d, J=6.7 Hz), 0.95 (3H, d, J=6.1 Hz), 1.40 (1H, dd,J=14.7, 10.4 Hz), 1.57 (1H, m), 1.68 (2H, m), 1.83 (1H, m), 2.30 (4H,m), 2.55 (2H, m), 2.63 (2H, m), 3.00 (1H, d, J=18.3 Hz), 3.06 (1H, d,J=6.7 Hz), 3.18 (1H, dt, J=13.4, 3.7 Hz), 4.3-5.2 (3H, br), 4.66 (1H, d,J=3.7 Hz), 6.46 (1H, d, J=7.9 Hz), 6.64 (1H, d, J=7.9 Hz); IR (neat); υ3350, 1609, 1460, 1249, 1118, 913 cm⁻¹; Mass (EI); m/z 398 (M+).

Example 3

17-Cyclopropylmethyl-14β-hydroxy-4,5α-epoxy-6α-methylaminomorphinan(yield: 75%) was obtained by following the procedure of example 1 butusing 3-dehydroxynaltrexone 3 instead of naltrexone hydrochloride.

NMR (500 MHz, CDCl₃); δ 0.13 (2H, m), 0.54 (2H, m), 0.75 (1H, m), 0.86(1H, m), 1.40 (1H, dd, J=14.7, 5.5 Hz), 1.57 (1H, m), 1.63 (1H, m), 1.72(2H, m), 2.25 (2H, m), 2.36 (2H, m), 2.52 (3H, s), 2.65 (2H, m), 3.08(3H, m), 4.70 (1H, dd, J=3.7, 1.8 Hz), 4.9-5.1 (1H, br), 6.56 (1H, d,J=7.9 Hz), 6.61 (1H, d, J=7.3 Hz), 7.04 (1H, t, J=7.9 Hz); IR (neat); υ3372, 1605, 1560, 1543, 1458, 1104, 864 cm⁻¹; Mass (EI); m/z 340 (M+).

Example 3

3-tert-butyldimethylsilyloxy-17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-methylaminomorphinan7 (yield: 50%) was obtained by following the procedure of example 1 butusing3-tert-butyldimethylsilyloxy-17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6-oxomorphinan2 instead of Naltrexone hydrochloride.

NMR (90 MHz, CDCl₃); δ 0.0-1.2 (5H, m), 0.19 (3H, s), 0.2 (3H, s), 1.0(9H, s), 1.3-1.9 (4H, m), 2.2-2.8 (7H, m), 2.56 (3H, s), 3.0 (1H, d,J=7.6 Hz), 3.0-3.3 (2H, m), 4.75 (1H, d, J=3.6 Hz), 6.5 (1H, d, J=7.2Hz), 6.63 (1H, d, J=7.2 Hz).

Example 4

6β-(N-Benzyl)methylamino-17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxymorphinan8

10.1 g of Naltrexone hydrochloride was separated with 150 ml of a 4:1solution of chloroform and methanol and 150 ml of saturated aqueoussodium bicarbonate. The aqueous layer was extracted twice with 100 ml ofa 4:1 solution of chloroform and methanol. The resulting organic layerwas dried with anhydrous sodium sulfate followed by the addition of 3.26g of benzoic acid and concentration after completely dissolving. Afteradequately drying the residue with a vacuum pump, the residue wassuspended in 400 ml of benzene. After adding 5.2 ml ofbenzylmethylamine, 4.9 g of benzoic acid and 0.23 g of p-toluenesulfonicacid, the resulting mixture was stirred for 18 hours in a 110° C. oilbath while boiling off the water. After distilling off 330 ml of benzeneat atmospheric pressure, 330 ml of ethanol and 4 g of molecular sieves4A were added to the reaction mixture followed by cooling to 0° C. Next,2.52 g of sodium cyanoborohydride was added followed by stirring for 2hours at room temperature. After adding 200 ml of methanol to thereaction system, the molecular sieves was filtered out and the filtratewas concentrated. 200 ml of chloroform and 150 ml of saturated aqueoussodium bicarbonate were added to the resulting residue and the resultingprecipitate was filtered followed by separation. The aqueous layer wasextracted twice with 100 ml of chloroform, and the organic layer wasconcentrated after drying with anhydrous sodium sulfate. The resultingcrude product was purified with silica gel column chromatography (480 gammonia saturated ammonium chloroform/chloroform=2/1) to obtain 10.87 gof the oily target compound (yield: 91%). This was then recrystallizedfrom methanol.

mp 71-80° C. (decomposition); NMR (400 MHz, CDCl₃); δ 0.09-0.13 (2H, m),0.49-0.55 (2H, m), 0.79-0.88 (1H, m), 1.25-1.35 (1H, m), 1.43-1.49 (1H,m), 1.59-1.66 (2H, m), 1.87-2.00 (1H, m), 2.11 (1H, dt, J=3.4, 11.7 Hz),2.19-2.27 (1H, m), 2.34 (3H, s), 2.35 (2H, d, J=6.8 Hz), 2.50-2.59 (1H,m), 2.56 (1H, dd, J=5.4, 18.1 Hz), 2.62 (1H, dd, J=4.4, 11.7 Hz), 2.99(1H, d, J=18.1 Hz), 3.04 (1H, d, J=5.4 Hz), 3.53 (1H, d, J=13.2 Hz),3.82 (1H, d, J=13.7 Hz), 4.68 (1H, d, J=8.3 Hz), 6.51 (1H, d, J=8.3 Hz),6.65 (1H, d, J=8.3 Hz), 7.20-7.35 (5H, m). IR (KBr); υ 3428, 3220, 1638,1615,1502, 1458, 1375, 1330, 1238, 1147, 1116, 1033, 990, 917, 857, 735cm⁻¹; Mass (EI); m/z 446 (M+), 355, 286, 160. Elementary Analysis: ASC₂₈H₃₄N₂O₃.0.5H₂O; Calculated values: C, 73.82; H, 7.74; N, 6.15.Measured values: C, 73.94; H, 7.79; N, 6.08.

Example 5

17-Cyclopropylmethyl-4,5α-epoxy-6β-(N-benzyl)ethylamino-3,14β-dihydroxymorphinan9 (yield: 46%) was obtained by following the procedure of example 4 butusing benzylethylamine instead of benzylmethylamine.

NMR (400 MHz, CDCl₃); δ 0.05-0.18 (2H, m), 0.46-0.58 (2H, m), 0.77-0.89(1H, m), 1.03 (3H, t, J=7.1 Hz), 1.22-1.33 (1H, m), 1.41-1.48 (1H, m),1.55-1.65 (2H, m), 1.86-1.99 (1H, m), 2.11 (1H, dt, J=3.9, 12.2 Hz),2.20 (1H, dt, J=4.9, 12.2 Hz), 2.33 (1H, dd, J=6.8, 12.7 Hz), 2.36 (1H,dd, J=6.8, 12.7 Hz), 2.50-2.75 (5H, m), 2.98 (1H, d, J=18.6 Hz), 3.03(1H, d, J=5.9 Hz), 3.56 (1H, d, J=14.4 Hz), 3.87 (1H, d, J=14.4 Hz),4.59 (1H, d, J=7.8 Hz), 4.85 (2H, brs), 6.50 (1H, d, J=7.8 Hz), 6.63(1H, d, J=7.8 Hz), 7.18-7.32 (3H, m), 7.40 (2H, d, J=6.8 Hz). Mass (EI);m/z 460 M+.

Example 617-Cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-methylaminomorphinan10

12.65 g of6β-(N-benzyl)methylamino-17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxymorphinan8·2 hydrochloride (converted to a hydrochloride by established methods)was dissolved in 250 ml of methanol followed by the addition of 2.53 gof 5% palladium-carbon and stirring for 4 hours in a hydrogenatmosphere. After removing the catalyst using Celite, the filtrate wasconcentrated. 100 ml of a 4:1 solution of chloroform and ethanol and 100ml of saturated aqueous sodium bicarbonate were added to the resultingresidue to separate, and the aqueous layer was then extracted twice with100 ml of a 4:1 solution of chloroform and ethanol. After drying theorganic layer with anhydrous sodium sulfate, the dried organic layer wasconcentrated to obtain 8.00 g of crude product. This was thenrecrystallized from methanol to obtain 5.84 g of the target compound(yield: 67%).

NMR (400 MHz, CDCl₃); δ 0.10-0.14 (2H, m), 0.50-0.55 (2H, m), 0.79-0.86(1H, m), 1.38 (1H, dt, J=2.9 Hz, 12.8 Hz), 1.41-1.48 (1H, m), 1.58-1.72(2H, m), 1.78-1.91 (1H, m), 2.08-2.25 (2H, m), 2.36 (1H, d, J=6.6 Hz),2.45 (3H, s), 2.49-2.65 (3H, m), 3.00 (1H, d, J=18.3 Hz), 3.05 (1H, d,J=5.9 Hz), 4.48 (1H, d, J=7.7 Hz), 6.54 (1H, d, J=8.1 Hz), 6.66 (1H, d,J=8.1 Hz). IR (KBr); υ 3380, 2926, 1638, 1607, 1462, 1255, 1180, 795cm⁻¹. Mass (EI); m/e 356 M+; Elementary Analysis: C₂₁H₂₈O₃N₂; Calculatedvalues: C, 70.76; H, 7.92; N, 7.86. Measured values: C, 70.51; H, 7.94;N, 7.84.

Example 7

17-Cyclopropylmethyl-4,5α-epoxy-6β-ethylamino-3,14β-dihydroxymorphinan11 (yield: 95%) was obtained by following the procedure of example 6 butusing6β-(N-benzyl)ethylamino-17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxymorphinan9·2 hydrochloride for the starting material instead of6β-(N-benzyl)methylamino-17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxymorphinan8·2 hydrochloride.

NMR (500 MHz, CDCl₃+D20); δ 0.08-0.17 (2H, m), 0.49-0.56 (2H, m),0.78-0.87 (1H, m), 1.16 (3H, t, J=7.1 Hz), 1.37 (1H, dt, J=2.9, 13.2Hz), 1.40-1.45 (1H, m), 1.57-1.61 (1H, m), 1.66-1.71 (1H, m), 1.83 (1H,dq, J=2.9, 13.2 Hz), 2.13 (1H, dt, J=12.1, 3.3 Hz), 2.20 (1H, dt,J=12.1, 4.8 Hz), 2.34 (1H, dd, J=12.8, 6.6 Hz), 2.37 (1H, dd, J=12.8,6.6 Hz), 2.52-2.69 (4H, m), 2.80 (1H, dq, J=11.4, 7.0 Hz), 3.00 (1H, d,J=18.3 Hz), 3.05 (1H, d, J=5.9 Hz), 4.46 (1H, d, J=7.7 Hz), 6.54 (1H, d,J=8.1 Hz), 6.67 (1H, d, J=8.1 Hz). Mass (EI); m/e 370 M+.

Reference Example 617-Allyl-3,14β-dihydroxy-4,5α-epoxy-6α-methylaminomorphinan 1217-Allyl-3,14β-dihydroxy-4,5α-epoxy-6β-methylaminomorphinan 13

Naloxone hydrochloride (3.0 g), methylamine hydrochloride (5.57 g) andsodium cyanoborohydride (0.33 g) were suspended in anhydrous methanol(40 ml) and stirred for 17 hours at room temperature. After addition ofconcentrated hydrochloric acid (1.0 ml) and removal of solvent bydistillation, distilled water (50 ml) was added followed by washing withchloroform (20 ml). Saturated aqueous sodium bicarbonate (10 ml) wasadded to make the solution basic followed by extraction with chloroform(30 ml×3). After drying with anhydrous magnesium sulfate, the solventwas distilled off. The resulting crude product was purified with silicagel column chromatography (Merk 7734 100 g; ethylacetate/methanol/aqueous ammonia=90/10/1->80/20/2) to obtain the targetcompound in the form of a pure fraction (12 0.4 g, 12%; 13 0.8 g, 24%).

Compound 12

NMR (400 MHz, CDCl₃); δ 0.87 (1H, m), 1.39 (1H, m), 1.66 (3H, m), 2,19(1H, dt, J=12.2, 4.9 hz), 2.29(1H, dt, J=12.7, 3.4 Hz), 2.55 (3H, m),2.59 (3H, s), 2.90 (1H, d, J=6.4 Hz), 3.09 (2H, m), 3.18 (1H, m), 4.76(1H, d, J=3.4 Hz), 4.7-4.9 (1H, br), 5.17 (2H, m), 5.80 (1H, m), 6.50(1H, d, J=7.8 Hz), 6.69 (1H, d, J=7.8 Hz); IR (neat); υ 3400, 1618,1450, 1386, 1160, 1067, 750 cm⁻¹. Mass (EI); m/z 342 (M+).

Compound 13

NMR (500 MHz, CDCl₃); δ 1.42 (2H, m), 1.61 (2H, m), 1.91 (1H, dq,J=12.8, 3.1 Hz), 2.16 (2H, m), 2.47 (3H, s), 2.56 (3H, m), 2.87 (1H, d,J=5.5 Hz), 3.03 (1H, d, J=18.3 Hz), 3.11 (2H, d, J=6.7 Hz), 4.51 (1H, 35d, J=7.9 Hz), 4.7-5.2 (3H, br), 5.18 (2H, m), 5.79 (1H, m), 6.55 (1H, d,J=7.9 Hz,), 6.64 (1H, d, J=7.9 Hz); IR (neat); υ 3400, 1560, 1543, 1458,1255, 1036, 731 cm⁻¹. Mass (EI); m/z 342 (M+).

Reference Example 7

17-Cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-methylamino)morphinan(yield: 40%) 14, and17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6β-(N-methylamino)morphinan(yield: 23%) 15 were obtained by following the procedure of referenceexample 6 but using17-cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-14β-hydroxy-3-methoxymorphinan-6-oneinstead of naloxone hydrochloride.

Compound 14

NMR (500 MHz, CDCl₃); δ 0.13-0.18 (2H, m), 0.53-0.59 (2H, m), 0.88 (1H,m), 1.78 (1H, d, J=7.8 Hz), 2.38 (2H, d, J=7.8 Hz), 2.40 (1H, d, J=6.3Hz), 2.44 (1H, dd, J=12.7, 6.3 Hz), 2.50 (1H, dd, J=18.6, 6.8 Hz), 2.58(3H, s), 2.72 (1H, d, J=7.8 Hz), 3.08 (1H, d, J=18.6 Hz), 3.35 (1H, d,J=6.8 Hz), 3.65 (1H, m), 3.84 (3H, s), 4.97 (1H, br), 4.99 (1H, dd,J=5.9, 1.5 Hz), 5.54 (1H, dd, J=9.8, 2.9 Hz), 5.88 (1H, dt, J=9.8, 1.5Hz), 6.51 (1H, d, J=7.8 Hz), 6.63 (1H, d, J=7.8 Hz). IR (neat); υ 3342,2938, 1508, 1456, 1284, 1205, 1123, 1054, 1017, 748 cm¹; Mass (EI); m/z368 (M+).

Compound 15

mp 121.5-123.5° C. (ethylacetate-ether); NMR (400 MHz, CDCl₃); δ0.09-0.16 (2H, m), 0.50-0.56 (2H, m), 0.84 (1H, m), 1.36 (1H, td,J=12.7, 3.9 Hz), 1.44 (1H, dd, J=12.7, 2.4 Hz), 1.61 (1H, dt, J=13.2,3.4 Hz), 1.66-1.83 (2H, m), 2.10 (1H, td, J=12.2, 3.9 Hz), 2.23 (1H, td,J=12.2, 4.9 Hz), 2.36 (2H, dd, J=6.4, 1.5 Hz), 2.43 (1H, m), 2.48 (3H,s), 2.57-2.66 (2H, m), 3.03 (1H, d, J=18.6 Hz), 3.08 (1H, d, J=5.9 Hz),3.87 (3H, s), 4.45 (1H, d, J=6.8 Hz), 6.61 (1H, d, J=8.3 Hz), 6.72 (1H,d, J=8.3 Hz). IR (KBr); υ 3390, 3344, 2944, 2802, 1632, 1611, 1504,1446, 1282, 1263, 1044, 980, 901 cm¹; Mass (EI); m/z 370 (M+).

Reference Example 83-tert-butyldimethylsilyloxy-17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylmethanesulfonamido)morphinan16

203.9 mg of3-tert-butyldimethylsilyloxy-17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-methylaminomorphinan7 obtained in reference example 5 was dissolved in 3 ml of pyridinefollowed by the addition of 124 mg of3,4-dichorophenylmethanesufonylchloride and stirring for 30 minutes atroom temperature. After concentrating the reaction system, 3 ml ofsaturated aqueous sodium bicarbonate and 3 ml of chloroform were addedto separate layers, after which the aqueous layer was extracted twicewith 3 ml of chloroform. After drying with anhydrous sodium sulfate, theorganic layer was concentrated to obtain the oily crude product. Thiswas then purified with silica gel column chromatography (30 gbenzene/ethyl acetate=5/1) to obtain 235.4 mg of the target compound(yield: 78%).

NMR (500 MHz, CDCl₃); δ 0.09-0.16 (2H, m), 0.15 (3H, s), 0.21 (3H, s),0.51-0.57 (2H, m), 0.80-0.89 (1H, m), 0.97 (9H, s), 1.21-1.30 (2H, m),1.42-1.49 (2H, m), 1.71 (1H, dt, J=14.7, 9.5 Hz), 2.15 (1H, dt, J=12.5,5.1 Hz), 2.22 (1H, dt, J=12.5, 3.7 Hz), 2.30 (1H, dd, J=12.8, 6.6 Hz),2.35 (1H, dd, J=12.8, 6.6 Hz), 2.56 (1H, dd, J=18.7, 7.0 Hz), 2.60-2.65(1H, m), 2.89 (3H, s), 3.01 (1H, d, J=18.7 Hz), 3.05 (1H, d, J=7.0 Hz),4.16 (1H, d, J=13.9 Hz), 4.19 (1H, d, J=13.9 Hz), 4.22-4.28 (1Hm), 4.41(1H, d, J=3.3 Hz), 4.90 (1H, brs), 6.48 (1H, d, J=8.1 Hz), 6.62 (1H, d,J=8.1 Hz), 7.31 (1H, dd, J=8.1, 2.2 Hz), 7.46 (1H, d, J=8.1 Hz), 7.53(1H, d, J=2.2 Hz). Mass (EI); m/z 692 M+.

Reference Example 9

3-tert-butyldimethylsilyloxy-17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-ethylphenylmethanesulfonamido)morphinan17 (yield: 50%) was obtained by following the procedure of referenceexample 8 but using phenylmethanesulfonylchloride instead of3,4-dichlorophenylmethanesulfonylchloride.

NMR (500 MHz, CDCl₃); δ 0.08-0.13 (2H, m), 0.14 (3H, S), 0.20 (3H, s),0.50-0.55 (2H, m), 0.79-0.87 (1H, m), 0.97 (9H, s), 1.10-1.22 (2H, m),1.37-1.43 (2H, m), 1.64 (1H, dt, J=15.0, 9.5 Hz), 2.12 (1H, dt, J=12.5,5.1 Hz), 2.20 (1H, dt, J=12.5, 3.3 Hz),2.29 (1H, dd, J=12.5, 6.6 Hz),2.33 (1H, dd, J=12.5, 6.6 Hz), 2.54 (1H, dd, J=18.7, 7.0 Hz), 2.59-2.63(1H, m), 2.83 (3H, S), 2.99 (1H, d, J=18.7 Hz), 3.02 (1H, d, J=7.0 Hz),4.19-4.24 (1H, m), 4.24 (1H, d, J=13.9 Hz), 4.28 (1H, d, J=13.9 Hz),4.34 (1H, d, J=2.9 Hz), 4.88 (1H, brs), 6.46 (1H, d, J=8.1 Hz), 6.61(1H, d, J=8.1 Hz), 7.32-7.40 (3H, m), 7.42-7.47 (2H, m). Mass (EI); m/z624 M+.

Reference Example 105β-Methylnaltrexone-O-methyloxime(17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-5β-methyl-6-methoxyiminomorphinan)18

109.3 mg of 5β-methylnaltrexone (0.326 mmol) and 37.2 mg of methoxyaminehydrochloride (0.445 mmol) were dissolved in 1.6 ml of methanol followedby the addition of 0.17 ml of 10% aqueous sodium hydroxide to thissolution and refluxing while heating. After 8.5 hours part way throughthe refluxing period, a solution of 36.1 mg (0.432 mmol) of methoxyaminehydrochloride in 0.5 ml of methanol was added and refluxing wascontinued until a total of 23 hours had elapsed. After allowing thereaction solution to cool to room temperature by standing, 5 ml of waterand 1 ml of saturated aqueous sodium bicarbonate were added followed byextraction with 2×5 ml of chloroform. The organic layers were combinedand dried with anhydrous sodium sulfate followed by concentration toobtain 107.4 mg of the unpurified target compound. This unpurifiedcompound was used in the following reaction without being purified.

NMR (400 MHz, CDCl₃); δ 0.13 (2H, m), 0.53 (2H, m), 0.84 (1H, m), 1.37(1H, m), 1.43 (1H, dd, J=14.1, 3.4 Hz), 1.62 (1H, m), 1.71 (3H, s),2.23-2.30 (3H, m), 2.30 (1H, br s, OH), 2.37 (2H, d, J=6.5 Hz), 2.55(1H, dd, J=18.3, 6.1 Hz), 2.71 (1H, m), 3.00 (1H, d, J=18.3 Hz), 3.04(1H, d, J=6.1 Hz), 3.14 (1H, ddd, J=14.7, 3.2, 3.2 Hz), 3.80 (3H, s),4.95 (1H, br s, OH), 6.55 (1H, d, J=8.0 Hz), 6.70 (1H, d, J=8.0 Hz). IR(KBr); υ 3380, 1638, 1620, 1510, 1460, 1377, 1336, 1241, 1118, 1038,953, 866, 752 cm⁻¹. Mass (EI); m/z 384 (M+).

Reference Example 1117-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-5β-methyl-6α-aminomorphinan19

101.0 mg (approximately 0.26 mmol) of the unpurified5β-methylnaltrexone-O-methyloxime 18 obtained in reference example 10was dissolved in 2.5 ml of anhydrous THF in the presence of argon gasfollowed by cooling to 0° C. After adding 1.31 ml of an anhydrous THFsolution of 1.0 M boraneTHF complex to this solution, the solution wasrefluxed for 18.5 hours while heating. After cooling the reactionsolution to 0° C. and slowly adding 10 ml of 2 N hydrochloric acid, thesolution was again refluxed for 40 minutes while heating. The reactionsolution was cooled to 0° C. followed by the addition of 4 ml of 5 Naqueous ammonia and 2 ml of saturated aqueous sodium bicarbonate, andextraction with 3×5 ml of chloroform-methanol (4:1). The organic layerswere combined and dried with anhydrous sodium sulfate followed byconcentration to obtain 89.6 mg of the unpurified target compound. Thisunpurified compound was then used in the following reaction withoutbeing purified.

NMR (400 MHz, CDCl₃); δ 0.12 (2H, m), 0.53 (2H, m), 0.83 (1H, m),1.37-1.84 (5H, m), 1.63 (3H, s), 2.15-2.28 (2H, m), 2.33 (2H, d, J=5.7Hz), 2.60 (1H, dd, J=18.5, 6.3 Hz), 2.67 (1H, m), 2.99 (1H, d, J=18.5Hz), 3.00 (3H, br s, OH, NH2), 3.02 (1H, d, J=6.3 Hz), 3.14 (1H, dd,J=8.8, 3.8 Hz), 4.90 (1H, br s, OH), 6.49 (1H, d, J=8.0 Hz), 6.63 (1H,d, J=8.0 Hz). IR (KBr); υ 3376, 3082, 1611, 1502, 1460, 1379, 1332,1245, 1122, 1038, 944, 868, 803 cm⁻¹. Mass (EI); m/z 356 (M+).

Example 86β-(N-Benzyl)methylamino-17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxymorphinan8

50.08 g (0.108 mol) of naltrexone benzoate was suspended in THF (350 ml)followed by the addition of 19.61 g (0.162 mol) of benzylmethylamine. ASoxhlet extractor containing molecular sieves 4A (50 g) was attachedfollowed by refluxing for 23 hours while heating. After adding methanol(200 ml) to the reaction system, 10.2 g (0.162 mol) of sodiumcyanoborohydride was dissolved in methanol (50 ml) and added to thereaction mixture followed by stirring for 30 minutes. After stirring,the solvent was distilled off and ethylacetate (400 ml) and 1% aqueoussodium bicarbonate (400 ml) were added to the residue to separatelayers. The aqueous layer was re-extracted with ethylacetate (80 ml).The resulting organic layer was washed with saturated brine (250 ml) andconcentrated after drying. Methanol (240 ml) was added to the resultingresidue to recrystallize and obtain 42.68 g of the target substance(yield: 88%). The data of this compound is the same as that shown inexample 4.

Example 9

An isomer mixture of17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6β-methylaminomorphinan 20 and17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6α-methylaminomorphinan 21(20:21=approximately 2:1, 44%) was obtained by following the procedureof example 8 but using 14-dehydroxynaltrexone instead of naltrexonebenzoate.

Mixture of Compound 20 and Compound 21

NMR (400 MHz, CDCl₃); δ 0.08-0.17 (2H, m), 0.49-0.55 (2H, m), 0.8-2.5(12H), 2.42 (2.lH, s), 2.54 (0.9H, s), 2.7-2.9 (2H), 3.36 (0.7H, m),3.41 (0.3H, m), 4.36 (0.7H, d, J=7.3 Hz), 4.78 (0.3H, d, J=2.9 Hz),6.48-6.56 (1H, m), 6.64-6.68 (1H, m) IR (neat); υ 2932, 1609, 1454,1325, 1259, 911, 731 cm⁻¹; Mass (EI); m/z 340 (M+).

Example 1017-Cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-methylaminomorphinan10]phthalate

42.58 g (0.0953 mol) of6β-(N-benzyl)methylamino-17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxymorphinan8 and 17.42 g (0.105 mol) of phthalic acid were dissolved in 500 ml ofmethanol followed by the addition of 12.7 g of 10% palladium-carbon andstirring for 12 hours in a hydrogen atmosphere. After the atmospherichydrogen was replaced to nitrogen, 300 ml of methanol was added followedby refluxing while heating. After dissolving the precipitated crystals,the catalyst was filtered out during heating using Celite. Afterdistilling off 200 ml of filtrate by atmospheric pressure condensation,the remaining filtrate was allowed to stand undisturbed to recrystallizeand obtain 26.82 g of the target compound (yield: 54%).

mp 151-164° C. (decomposition); NMR (400 MHz, D20); δ 0.40-0.50 (2H, m),0.73 (1H, m), 0.82 (1H, m), 1.08 (1H, m), 1.56 (1H, m), 1.67 (1H, m),1.85 (1H, m), 1.89-2.02 (2H, m), 2.52 (1H, ddd, J=13.2, 13.2, 4.9 Hz),2.75 (1H, ddd, J=12.9, 12.9, 4.2 Hz), 2.78 (3H, s), 2.93-3.04 (2H, m),3.16-3.25 (2H, m), 3.32-3.43 (2H, m), 4.07 (1H, br d, J=5.9 Hz), 4.99(1H, d, J=7.3 Hz), 6.85 (1H, d, J=8.0 Hz), 6.90 (1H, d, J=8.0 Hz),7.34-7.39 (2H, m), 7.43-7.48 (2H, m). IR (KBr); υ 3388, 3032, 1605,1557, 1510, 1460, 1367, 1330, 1243, 1168, 1120, 1035, 992, 936, 859, 770cm⁻¹. Mass (FAB); m/z 357 ((M+H)+). Elementary Analysis: AsC₂₁H₂₈N₂O₃.C₈H₆O₄.0.8H₂O; Calcd.: C, 64.86; H, 6.68; N, 5.22. Found.: C,64.93; H, 6.61; N, 5.23.

Example 1117-Cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylacetoamido)morphinan.hydrochlorid

8.9 g of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinanA obtained in example 1 was dissolved in 180 ml of chloroform. Afteradding 10.4 ml of triethylamine, 10.4 ml of 3,4-dichlorophenylacetylchloride (obtained by converting commercially available carboxylic acidinto an acid chloride by established methods) was added dropwise at 0°C. After completion of dropwise addition, the reaction solution wasstirred for 1 hour at room temperature followed by the addition of 150ml of saturated aqueous sodium bicarbonate to the reaction system toseparate. The aqueous layer was then extracted twice with 100 ml ofchloroform. After drying with anhydrous sodium sulfate, the organiclayer was concentrated. The resulting residue was dissolved in a mixedsolvent of 140 ml of methanol and 14 ml of chloroform followed by theaddition of 1.7 g of potassium carbonate at room temperature andstirring for 30 minutes. 100 ml of water and 350 ml of chloroform werethen added to the reaction solution to separate layers, and the aqueouslayer was extracted twice with 80 ml of chloroform. After drying withanhydrous sodium sulfate, the resulting organic layer was concentrated.The resulting residue was recrystallized from a 2:1 mixture ofethylacetate and methanol to obtain 8.15 g of the free base form. Thiswas then dissolved in a mixed solvent of chloroform and methanolfollowed by concentration after adjusting to pH 3 by addition ofmethanol solution of hydrochloride. This solution was re-precipitatedfrom chloroform, methanol and ether to obtain 8.44 g of the targetcompound (yield: 58%).

mp 252-254° C.; NMR (400 MHz, DMSO-d₆); δ 0.43 (2H, m), 0.65 (2H, m),1.05 (1H, m), 1.16 (1.5H, m), 1.37 (1H, m), 1.58 (2H, m), 1.92 (1H, m),2.43 (1H, m), 2.68 (1H, m), 2.81 (0.5H, s), 2.96 (2.5H, s), 3.05 (2.5H,m), 3.30 (2H, m), 3.85 (3H, m), 4.48 (0.2H, m), 4.62 (0.8H, d, J=3.9Hz), 4.75 (0.2H, m), 4.96 (0.8H, m), 6.21 (0.8H, m), 6.46 (0.2H, m),6.58 (1H, d, J=8.3 Hz), 6.72 (1H, d, J=8.3 Hz), 7.25 (1H, m), 7.55 (2H,m), 8.80 (1H, brs), 9.32 (1H, brs); IR (KBr); υ 3370, 1620, 1510, 1473,1120, 1035, cm⁻¹. Mass (FABS); m/z 543 (M+H)+; Elementary Analysis: AsC₂₉H₃₂N₂O₄Cl₂.HCl.0.5H₂O; Calcd.: C, 59.14; H, 5.82; N, 4.75; Cl, 18.06;Found.: C, 59.34; H, 5.78; N, 4.78; Cl, 17.78.

Examples 12-40

17-Cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-phenylpropionamido)morphinantartrate22 (yield: 84%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methylphenylacetamido)morphinanhydrochloride23 (yield: 70%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methylcinnamamido)morphinan-hydrochloride24 (yield: 74%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methylacetamido)morphinanhydrochloride25 (yield: 93%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-bromophenylacetamido)morphinan.hydrobromate 26 (yield: 85%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3,4-dichlorobenzamido)morphinanhydrochloride 27 (yield: 58%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-4-bromophenylacetamido)morphinanehydrobromide28 (yield: 73%),17-cyclopropylmethyl-4,5α-epoxy-3,140-dihydroxy-6α-[(R)-N-methyl-2-phenylpropionamido]morphinan.hydrochloride29 (yield: 52%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[(R)-N-methylmethoxyphenylacetamido]morphinan.hydrochloride30 (yield: 98%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[(S)-N-methylmethoxyphenylacetamido]morphinanhydrochloride31 (yield: 70%),17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[(S)-N-methyl-2-phenylpropionamido]morphinan.tartrate 3 (yield: 85%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methylcyclohexylcarboxyamido)morphinan.hydrochloride 33 (yield: 58%),17-cyclopropylmethyl-3,140-dihydroxy-4,5α-epoxy-6α-(N-methylbenzamido)morphinan.hydrochloride 34 (yield: 52%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-4-phenylbutyramido)morphinan.hydrochloride35 (yield: 80%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-6-phenylhexanamido)morphinan.hydrochloride36 (yield: 63%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-fluorophenylacetamido)morphinan.hydrochloride37 (yield: 57%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methylphenoxyacetamido)morphinan.hydrochloride 3 (yield: 86%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methylhexanamido)morphinan.tartrate39 (yield: 68%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methylheptanamido)morphinan.tartrate40 (yield: 81%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[N-methyl-3-(3-pyridyl)propionamido]morphinan.tartrate41 (yield: 65%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methylbenzyloxycarbamido)morphinan.tartrate42 (yield: 61%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-4-nitrobenzyloxycarbamido)morphinan.hydrochloride43 (yield: 68%),17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-(3-pyridyl)methyloxycarbamido]morphinan.tartrate44 (yield: 31%),17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylthiophenoxyacetamido)morphinan.tartrate45 (yield: 50%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methylheptanamido)morphinan.hydrochloride46 (yield: 62%),17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylbutyroxycarbamido)morphinane.tartrate47 (yield: 70%),17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3-cyclopentylpropionamido)morphinantar.trate 48 (yield: 84%),17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-2-methoxyethoxycarbamido)morphinan.tartrate49 (yield: 70%), and17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-trans-3-cyclohexylacrylamido)morphinan.hydrochloride5 (yield: 72%) were obtained by following the procedure of example 11,but using 3-phenylpropionyl chloride, phenylacetyl chloride,trans-cinnamoyl chloride, acetyl chloride, 3-bromophenylacetyl chloride,3,4-dichlorobenzoyl chloride, 4-bromophenylacetyl chloride,R-(−)-2-phenylpropionyl chloride, R-(−)-methoxyphenylacetyl chloride,S-(+)-methoxyphenylacetyl chloride, S-(+)-2-phenylpropionyl chloride,cyclohexanecarbonyl chloride, benzoyl chloride, 4-phenylbutanoylchloride, 6-phenylhexanoyl chloride, 3-fluorophenylacetyl chloride,phenoxyacetyl chloride, hexanoyl chloride, heptanoyl chloride,3-(3-pyridyl)propionyl chloride, benzyl chloroformate, 4-nitrobenzylchloroformate, 3-pyridylmethyl chloroformate, thiophenoxyacetylchloride, heptanoyl chloride, butyl chloroformate,3-cyclopentylpropionyl chloride, 2-methoxyethyl chloroformate andtrans-3-cyclohexylacryloyl chloride instead of 3,4-dichlorophenylacetylchloride.

Compound 22

mp >203° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.13-0.27 (2H,m), 0.47-0.59 (2H, m), 0.80-0.95 (1H, m), 1.06-1.57 (5H, m), 1.68-1.79(1H, m), 1.95-2.33 (2H, m), 2.57-2.89 (6H, m), 2.88 (2.1H, s), 3.17(0.9H, s), 3.00-3.53 (3H, m), 3.45 (3H, brs), 4.09 (1H, s), 4.29-4.36(0.3H, m), 4.54 (0.7H, d, J=3.7 Hz). 4.54-4.59 (0.3H, m), 4.92 (0.7H,m), 6.51 (0.7H, d, J=8.0 Hz), 6.49-6.52 (0.3H, m), 6.62 (1H, d, J=8.0Hz), 7.05-7.31 (5H, m), 9.10 (1H, brs). IR (KBr); υ 3420, 1605, 1460,1174, 1120, 1073, 1036 cm⁻¹. Mass (EI); m/z=488 M+. Elementary Analysis:As C₃₀H₃₆N₂O₄.0.5C₄H₆O₆.0.2.2H₂O; Calcd.: C, 67.75; H, 7.00; N, 4.94.Found.: C, 67.79; H, 7.09; N, 5.04.

Compound 23

mp 253.0-257.0° C. (decomposition, ether); NMR (400 MHz, DMSO-d₆); δ0.40 (1H, m), 0.47 (1H, m), 0.60 (1H, m), 0.69 (1H, m), 1.05 (1H, m),1.09 (1H, m), 1.34 (1H, m), 1.47 (1H, m), 1.56 (1H, dd, J=14.7, 9.3 Hz),1.61 (1H, d, J=13.7 Hz), 1.91 (1H, m), 2.36-2.52 (2H, m), 2.69 (1H, m),2.80 (0.8H, s), 2.93 (1H, m), 2.95 (2.2H, s), 3.15 (1H, d, J=12.2 Hz),3.09 (1H, dd, J=19.8, 7.1 Hz), 3.76 (2H, s), 3.89 (1H, br s), 4.27(0.27H, s), 4.51 (0.27H, m), 4.63 (0.73H, d, J=3.4 Hz), 5.00 (0.73H, dt,J=13.7, 3.4 Hz), 6.20 (0.73H, brs), 6.40 (0.27H, m), 6.58 (1H, d, J=8.3Hz), 6.72 (1H, dd, J=8.3, 2.0 Hz), 7.22-7.29 (2H, m), 7.30-7.38 (3H, m),8.80 (1H, br s), 9.29 (1H, d, J=5.9 Hz). IR (KBr); υ 3400, 3100, 2952,1620, 1508, 1475, 1319, 1120, 1036, 806 cm⁻¹. Mass (FAB); m/z 475(M+H)+. Elementary Analysis: As C₂₉H₃₅N₂O₄Cl.0.3H₂O; Calcd.: C, 67.44;H, 6.95; N, 5.43; Cl, 6.86. Found.: C, 67.45; H, 7.15; N, 5.40; Cl,6.99.

Compound 24

mp 254-257° C.; NMR (400 MHz, DMSO-d₆); δ 0.21 (2H, m), 0.52 (2H, m),0.91 (1H, m), 1.20 (1.5H, m), 1.48 (3H, m), 1.78 (1H, m), 2.26 (2.5H,m), 2.58 (1H, m), 2.73 (2H, m), 2.91 (0.5H, s), 3.06 (1H, m), 3.09(2.5H, m), 3.20-3.90 (4H, br), 4.03 (1H, s), 4.5-5.1 (2H, m), 6.52 (1H,d, J=7.9 Hz), 6.62 (1H, d, J=7.9 Hz), 7.09 (0.2H, d, J=15.9 Hz), 7.23(0.8H, d, J=15.9 Hz), 7.40-7.60 (4H, m), 7.60-7.80 (2H, m), 8.80-9.20(1H, br). IR (KBr); υ 3400, 1644, 1593, 1317, 1118, 1038, 768 cm⁻. Mass(FAB); m/z 487 (M+H); Elementary Analysis: As C₃₂H₃₇N₂O₇.0.8H₂O; Calcd.:C, 66.72; H, 6.75; N, 4.86; Found.: C, 66.56; H, 6.74; N, 5.08.

Compound 25

mp >300.0° C. (decomposition, ether); NMR (400 MHz, DMSO-d₆); δ 5 0.40(1H, m), 0.48 (1H, m), 0.61 (1H, m), 0.69 (1H, m), 1.05 (1H, m), 1.13(1H, m), 1.33 (1H, m), 1.55 (1H, dd, J=15.3, 9.8 Hz), 1.59 (1H, d,J=14.0 Hz),1.92 (1H, dt, J=15.3, 9.5 Hz), 2.05 (2.5H, s), 2.13 (0.5H,s), 2.43 (1H, dt, J=13.4, 4.9 Hz), 2.69 (1H, m), 2.77 (0.5H, s), 2.89(2.5H, s), 2.94 (1H, dd, J=13.1, 7.0 Hz), 3.03 (1H, br d, J=10.3 Hz),3.09 (1H, dd, J=20.1, 7.3 Hz), 3.24-3.38 (2H, m), 3.91 (1H, d, J=6.7Hz), 4.37 (0.17H, br d, J=12.2 Hz), 4.61 (0.83H, d, J=4.3 Hz), 4.81(0.17H, d, J=4.3 Hz), 4.94 (0.83H, dt, J=14.0, 3.7 Hz), 6.26 (0.83H, s),6.46 (0.17H, s), 6.58 (1H, d, J=8.2 Hz), 6.73 (1H, dd, J=8.2, 1.8 Hz),8.82 (1H, br s), 9.31 (1H, s). IR (KBr); υ 3400, 3100, 2866, 1618, 1500,1301, 1172, 1120, 1038, 920 cm⁻¹. Mass (FAB); m/z 399 (M+H)+. ElementaryAnalysis: As C₂₃H₃₀N₂O₄.1.12HCl.0.5H₂O; Calcd.: C, 61.61; H, 7.22; N,6.25; Cl, 8.86. Found.: C, 61.43; H, 7.21; N, 6.33; Cl, 9.00.

Compound 26

mp 200.0-205.0° C. (decomposition, ether); NMR (400 MHz, DMSO-d₆); δ0.40 (1H, m), 0.46 (1H, m), 0.60 (1H, m), 0.68 (1H, m), 1.03 (1H, m),1.15 (1H, m), 1.36 (1H, m), 1.53-1.65 (2H, m), 1.87 (1H, m), 2.41 (1H,m), 2.68 (1H, m), 2.80 (0.4H, s), 2.96 (2.6H, s), 2.87-3.12 (3H, m),3.20-3.35 (2H, m), 3.79 (2H, s), 3.85 (1H, m), 4.63 (0.87H, d, J=3.4Hz), 4.65 (0.13H, m), 4.97 (1H, dt, J=13.7, 3.4 Hz), 6.13 (0.87H, s),6.22 (0.13H, s), 6.59 (1H, d, J=8.3 Hz), 6.71 (1H, d, J=8.3 Hz), 7.25(1H, d, J=7.8 Hz), 7.29 (1H, t, J=7.8 Hz), 7.45 (1H, d, J=7.8 Hz), 7.46(1H, s), 8.76 (1H, br s), 9.29 (1H, s). IR (KBr); υ 3400, 2952, 1626,1506, 1407, 1319, 1120, 1036, 919, 772, 748 cm⁻¹; Mass (FAB); m/z 553(M+H)+. Elementary Analysis: As C₂₉H₃₄N₂O₄Br₂.0.4H₂O; Calcd.: C, 54.29;H, 5.48; N, 4.37; Br, 24.91. Found.: C, 54.04; H, 5.63; N, 4.34; Br,25.19.

Compound 27

mp 230° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.32-0.74 (4H, m),0.93-1.11 (1H, m), 1.12-1.42 (2H, m), 1.45-1.78 (3H, m), 1.94-2.22 (1H,m), 2.65-2.76 (1H, m), 2.86 (2.4H, s), 2.91-3.15 (3.6H, m), 3.20-3.40(2H, m), 3.79 (0.2H, m), 3.94 (0.8H, m), 4.24 (0.2H, m), 4.62 (0.2H, m),4.85 (0.8H, m), 4.98 (0.8H, m), 5.97 (0.2H, br s), 6.35 (0.8H, br s),6.59 (1H, d, J=7.9 Hz), 6.73 (1H, d, J=7.9 Hz), 7.40-7.50 (1H, m),7.69-7.79 (2H, m), 8.66 (0.2H, br s), 8.88 (0.8H, br s), 9.31 (0.8H, brs), 9.38 (0.2H, br s). IR (KBr); υ 3152, 1626, 1508, 1473, 1408, 1379,1315, 1033 cm⁻¹. Mass (FAB); m/z 529 ((M+H)+). Elementary Analysis: AsC₂₈H₃₀N₂O₄Cl₂.HCl.0.2H₂O; Calcd.: C, 59.05; H, 5.56; N, 4.92; Cl, 18.67.Found.: C, 58.93; H, 5.68; N, 4.90; Cl 18.54.

Compound 28

mp 210° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.45 (2H, m), 0.64(2H, m), 1.07 (1H, m), 1.15 (2H, m), 1.35 (1H, m), 1.58 (2H, m), 1.90(1H, m), 2.42 (1H, m), 2.67 (1H, m), 2.80 (0.5H, s), 2.92 (1H, m), 2.95(2.5H, s), 3.10 (2H, m), 3.31 (1H, m), 3.80 (3H, m), 4.4-5.0 (2H, m),6.14 (0.8H, brs), 6.23 (0.2H, brs), 6.59 (1H, d, J=8.6 Hz), 6.72 (1H, d,J=8.6 Hz), 7.21 (2H, m), 7.52 (2H, m), 8.76 (1H, brs), 9.0-9.5 (1H, br);IR (KBr); υ 3320, 1620, 1466, 1321, 1120, 803 cm⁻¹. Mass (FAB); m/z 553(M+H); Elementary Analysis: As C₂₉H₃₃N₂O₄Br.HBr.0.5H₂O; Calcd.: C,54.14; H, 5.48; N, 4.35; Br, 24.84; Found.: C, 53.90; H, 5.42; N, 4.30;Br, 25.21.

Compound 29

mp >203° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.35-0.75 (4H,m), 1.07-1.15 (3H, m), 1.33 (3H, d, J=6.8 Hz), 1.40-1.67 (2H, m),1.84-2.15 (1.4H, m), 2.43-2.75 (0.6H, m), 2.80 (0.9H, s), 2.81 (2.1H,s), 2.90-3.15 (3H, m), 3.20-3.50 (3H, m), 3.85-3.95 (1H, m), 4.12-4.28(1H, m), 4.53-4.70 (1.3H, m), 4.95-5.05 (0.7H, m), 6.25 (0.7H, brs),6.40-6.60 (1.3H, m), 6.66 (0.3H, d, J=8.3 Hz), 6.71 (0.7H, d, J=7.8 Hz),7.18-7.42 (5H, m), 8.80-8.95 (1H, brs), 9,21 (0.3H, s), 9.30 (0.7H, s).IR (KBr); υ 3420, 1620, 1508, 1460, 1120, 1067, 1036, 704 cm⁻¹; Mass(FAB); m/z 489 (M+H)+. Elementary Analysis: As C₃₀H₃₆N₂O₄.HCl.0.3H₂O;Calcd.: C, 67.92; H, 7.14; N ,5.28; Cl, 6.68. Found.: C, 68.05; H, 7.21;N, 5.39; Cl, 6.31.

Compound 30

mp 207.0-211.0° C. (decomposition, ether); NMR (400 MHz, DMSO-d₆); δ0.39 (1H, m), 0.47 (1H, m), 0.61 (1H m), 0.68 (1H, m), 1.07 (1H, m),1.22 (1H, m), 1.39 (1H, m), 1.50 (1H, dd, J=15.1, 9.3 Hz), 1.63 (1H, d,J=11.2 Hz), 1.90 (1H, m), 2.30 (0.15H, dt, J=13.2, 4.9 Hz), 2.47 (0.85H,dt, J=13.2, 4.9 Hz), 2.64 (1H, m), 2.81 (0.45H, s), 2.88 (2.55H, s),2.95-3.10 (3H, m), 3.20-3.35 (2H, m), 3.30 (0.45H, s), 3.40 (2.55H, s),3.78 (0.15H, br s), 3.92 (0.85H, br d, J=6.8 Hz), 4.64 (0.15H, br d,J=12.7 Hz), 4.69 (1H, d, J=3.4 Hz), 4.95 (0.85H, br d, J=13.7 Hz), 5.26(0.85H, s), 5.35 (0.15H, s), 6.28 (0.85H, s), 6.54 (0.15H, d, J=8.3 Hz),6.57 (0.85H, d, J=8.3 Hz), 6.63 (0.15H, s), 6.69 (0.15H, d, J=8.3 Hz),6.72 (0.85H, d, J=8.3 Hz), 7.31-7.46 (5H, m), 8.86 (0.85H, br s), 8.92(0.15H, br s), 9,27 (0.15H, s), 9.34 (0.85H, s). IR (KBr); υ 3400, 1638,1460, 1321, 1120, 1035, 600, 418 cm⁻¹; Mass (FAB); m/z 505 (M+H)+.Elementary Analysis: As C₃₀H₃₇N₂O₅Cl.0.4H₂O; Calcd.: C, 65.72; H, 6.95;N, 5.11; Cl, 6.47. Found.: C, 65.77; H, 7.14; N, 5.23; Cl, 6.41.

Compound 31

mp 270.0-275.0° C. (decomposition, ether); NMR (400 MHz, DMSO-d₆); δ0.40 (1H, m), 0.48 (1H, m), 0.62 (1H, m), 0.69 (1H, m), 1.07 (1H, m),1.11 (1H, m), 1.35 (1H, m), 1.50 (1H, t, J=14.5 Hz), 1.57 (1H, t, J=15.6Hz), 1.86 (0.22H, m), 1.97 (0.78H, m), 2.44 (1H, dt, J=13.2, 4.4 Hz),2.66 (1H, m), 2.80 (0.66H, s), 2.88 (2.34H, s), 2.96-3.12 (3H, m),3.24-3.37 (2H, m), 3.30 (2.34H, s), 3.38 (0.66H, s), 3.92 (1H, d, J=5.9Hz), 4.27 (0.22H, d, J=1.5 Hz), 4.56 (0.78H, d, J=3.4 Hz), 4.75 (0.22H,m), 5.07 (0.78H, br d, J=13.7 Hz), 5.19 (0.78H, s), 5.24 (0.22H, s),6.31 (0.78H, s), 6.50 (0.22H, s), 6.56 (1H, d, J=8.3 Hz), 6.71 (1H, d,J=8.3 Hz), 7.34-7.43 (5H, m), 8.85 (1H, br s), 9.27 (0.78H, s), 9.30(0.22H, s). IR (KBr); υ 3500, 3100, 2942, 2346, 1638, 1508 1475, 1319,1176, 1120, 1036, 905 cm⁻¹. Mass (FAB); m/z 505 (M+H)+. ElementaryAnalysis: As C₃₀H₃₇N₂O₅Cl.0.3H₂O; Calcd.: C, 65.93; H, 6.94; N, 5.13;Cl, 6.49. Found.: C, 65.89; H, 7.02; N, 5.12; Cl, 6.53.

Compound 32

mp 162-165° C. NMR (400 MHz, DMSO-d₆); δ 0.21 (2H, m), 0.53 (2H, m),0.91 (1H, m), 1.09 (1H, m), 1.28 (3H, d, J=6.4 Hz), 1.3-1.5 (3.3H, m),1.75 (0.7H, m), 2.2-2.3 (2H, m), 2.4-2.8 (4H, m), 2.78 (1H, s), 2.84(2H, s), 3.0-3.3 (2H, m), 4.04 (1H, s), 4.0-4.1 (1H, m), 4.4-5.1 (2H,m), 6.47 (1H, m), 6.59 (1H, m), 7.2-7.4 (5H, m); IR (KBr); υ 3400, 1620,1462, 1120, 1067, 702 cm⁻¹. Mass (FAB); m/z 489 (M+H); ElementaryAnalysis: As C₃₂H₃₉N₂O₇.0.4H₂O; Calcd.: C, 67.33; H, 7.03; N, 4.91;Found.: C, 67.28; H. 7.26; N, 4.90.

Compound 33

mp >260° C. (decomposition, methanol-ether); NMR (400 MHz, CD₃OD; dataonly for major amide form (approximately 90%)); δ 0.49 (2H, m), 0.73(1H, m), 0.83 (1H, m), 1.08 (1H, m), 1.22-1.57 (7H, m), 1.62-1.98 (8H,m), 2.57-2.74 (2H, m), 2.83-3.02 (2H, m), 3.04-3.20 (2H, m), 3.06 (3H,s), 3.22-3.39 (2H, m), 3.97 (1H, m), 4.74 (1H, m), 5.08 (1H, ddd,J=14.7, 3.9, 3.9 Hz), 6.67 (1H, d, J=8.3 Hz), 6.75 (1H, d, J=8.3 Hz). IR(KBr); υ 3366, 1607, 1510, 1473, 1319, 1197, 1118, 1038, 907, 804 cm⁻¹.Mass (FAB); m/z 467 ((M+H)+). Elementary Analysis: As C₂₈H₃₈N₂O₄.HCl;Calcd.: C, 66.85; H, 7.81; N 5.57; Cl, 7.05. Found.: C, 66.87; H, 7.90;N, 5.53; Cl, 7.03.

Compound 34

mp 235° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.35-0.76 (4H, m),0.96-1.14 (1H, m), 1.16-1.42 (2H, m), 1.43-1.82 (3H, m), 1.96-2.20 (1H,m), 2.58-2.77 (1H, m), 2.78-3.07 (6H, m), 3.20-3.35 (2H, m), 3.79 (0.2H,m), 3.96 (0.8H, m), 4.35 (0.2H, m), 4.58 (0.2H, m), 4.87 (0.8H, m), 5.01(0.8H, m), 5.95 (0.2H, br s), 6.38 (0.8H, br s), 6.59 (1H, d, J=7.3 Hz),6.73 (1H, d, J=7.3 Hz), 7.40-7.50 (5H, m), 8.63 (0.2H, br s), 8.88(0.8H, br s), 9.31 (0.8H, br s), 9.38 (0.2H, br s). IR (KBr); υ 3270,3072, 1613, 1506, 1475, 1321, 1120, 1069, 905, 806, 710 cm⁻¹; Mass(FAB); m/z 461 ((M+H)+). Elementary Analysis: As C₂₈H₃₂N₂ ₄.HCl.0.7H₂O;Calcd.: C, 65.99; H, 6.80; N, 5.49; Cl, 6.96. Found.: C, 65.97; H, 6.86;N, 5.55; Cl, 6.94.

Compound 35

mp 235° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.40 (1H, m), 0.47(1H, m), 0.61 (1H, m), 0.68 (1H, m), 1.01-1.09 (2H, m), 1.36 (1H, m),1.50-1.64 (2H, m), 1.80-1.98 (3H, m), 2.34-2.46 (3H, m), 2.60-2.75 (3H,m), 2.80 (0.6H, s), 2.85 (2.4H, s), 2.88-3.14 (3H, m), 3.22-3.35 (2H,m), 3.90 (1H, m), 4.41 (0.2H, m), 4.61 (0.8H, d, J=3.9 Hz), 4.68 (0.2H,m), 4.97 (0.8H, m), 6.24 (0.8H, br s), 6.46 (0.2H, br s), 6.58 (1H, d,J=8.1 Hz), 6.75 (1H, m), 7.16-7.26 (3H, m), 7.30 (2H, m), 8.82 (1H, brs), 9.30 (0.8H, s), 9.33 (0.2H, s). IR (KBr); υ 3068, 1618, 1508, 1475,1369, 1317, 1118, 1036, 919, 806, 750, 704 cm⁻¹. Mass (FAB); m/z 503((M+H)+). Elementary Analysis: As C₃₁H₃₈N₂O₄.HCl Calcd.: C, 69.06; H,7.29; N, 5.19; Cl, 6.58. Found.: C, 69.05; H, 7.43; N, 5.27; Cl, 6.43.

Compound 36

mp 225° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.40 (1H, m), 0.47(1H, m), 0.61 (1H, m), 0.68 (1H, m), 1.01-1.20 (2H, m), 1.25-1.37 (3H,m), 1.50-1.64 (6H, m), 1.91 (1H, m), 2.33 (2H, t, J=7.1 Hz), 2.42 (1H,m), 2.58 (2H, t, J=7.5 Hz), 2.68 (1H, m), 2.78 (0.6H, s), 2.87 (2.4H,s), 2.93 (1H, m), 2.99-3.14 (2H, m), 3.24-3.35 (2H, m), 3.89 (1H, m),4.42 (0.2H, m), 4.59 (0.8H, d, J=3.4 Hz), 4.76 (0.2H, m), 4.96 (0.8H,m), 6.22 (0.8H, s), 6.44 (0.2H, s), 6.58 (1H, d, J=7.8 Hz), 6.72 (1H, d,J=7.8 Hz), 7.16-7.23 (3H, m), 7.24-7.30 (2H, m), 8.81 (1H, br s), 9.29(0.8H, s), 9.31 (0.2H, s). IR (KBr); υ 3086, 1618, 1508, 1460, 1315,1174, 1120, 1038, 748, 700 cm⁻¹. Mass (FAB); m/z 531 ((M+H)+).Elementary Analysis: As C₃₃H₄₂N₂O₄.HCl; Calcd.: C, 69.88; H, 7.64; N,4.94; Cl, 6.25. Found.: C, 69.70; H, 7.64; N, 4.98; Cl, 6.25.

Compound 37

mp 225° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.40 (1H, m), 0.47(1H, m), 0.61 (1H, m), 0.69 (1H, m), 1.01-1.20 (2H, m), 1.35 (1H, m),1.50-1.64 (2H, m), 1.90 (1H, m), 2.41 (1H, m), 2.67 (1H, m), 2.70 (0.6H,s), 2.95 (2.4H, s), 2.89-3.13 (3H, m), 3.23-3.35 (2H, m), 3.80 (1.6H,s), 3.85-3.94 (1.4H, m), 4.47 (0.2H, m), 4.51 (0.2H, m), 4.63 (0.8H, d,J=3.9 Hz), 4.98 (0.8H, m), 6.20 (0.8H, s), 6.43 (0.2H, br s), 6.58 (1H,d, J=8.3 Hz), 6.72 (1H, d, J=8.3 Hz), 7.05-7.15 (3H, m), 7.35 (1H, m),8.80 (1H, br s), 9.30 (0.2H, s), 9.31 (0.8H, s). IR (KBr); υ 3120, 1620,1510, 1460, 1321, 1118, 777, 683, 518 cm⁻¹. Mass (FAB); m/z 493((M+H)+); Elementary Analysis: As C₂₉H₃₃N₂O₄F.HCl; Calcd.: C, 65.83; H,6.48; N, 5.29; Cl, 6.70; F, 3.59. Found.: C, 65.69; H, 6.59; N, 5.44;Cl, 6.43; F. 3.60.

Compound 38

mp 198.0-206.0° C. (decomposition, diethylether); NMR (400 MHz,DMSO-d₆); δ 0.10-0.30 (2H, m), 0.44-0.63 (2H, m), 0.83-0.99 (1H, m),0.90-1.28 (1H, m), 1.28-1.39 (1H, m), 1.39-1.57 (2H, m), 1.66-1.84 (1H,m), 2.12-2.38 (2H, m), 2.41-2.65 (2H, m), 2.65-2.80 (2H, m), 2.84 (0.6H,s), 2.95 (2.4H, s), 3.00-3.13 (1H, m), 3.20-3.34 (1H, m), 2.50-4.25 (3H,br s), 4.05 (1H, s), 4.38 (0.2H, dt J=11.2, 3.4 Hz), 4.54 (0.8H, d,J=3.4 Hz), 4.85 (2H, s), 4.76-4.96 (1H, m), 6.51 (1H, d, J=7.8 Hz), 6.64(1H, d, J=8.3 Hz), 6.86-7.02 (3H, m), 7.22-7.37 (2H, m), 8.65-9.60 (1H,br s); IR (KBr); υ 1601, 1562, 1497, 1460, 1321, 1236, 1120, 1067, 919,758 cm⁻¹; Mass (FAB); m/z 491 ((M+H)). Elementary Analysis: AsC₃₁H₃₇N₂O₈.0.8H₂O; Calcd.: C, 64.19; H, 6.70; N, 4.83; Found.: C, 64.16;H. 6.64; N, 4.89.

Compound 39

mp 205-207° C.; NMR (400 MHz, DMSO-d₆); δ 0.18-0.30 (2H, m), 0.47-0.60(2H, m), 0.82-0.97 (4H, m), 1.13 (1H, m), 1.24-1.38 (5H, m), 1.38-1.60(4H, m), 1.75 (1H, m), 2.20-2.40 (4H, m), 2.57 (1H, m), 2.70-2.79 (3H,m), 2.80 (0.6H, s), 2.88 (2.4H, s), 3.00-3.63 (5H, m), 4.10 (1H, s),4.36 (0.2H, m), 4.53 (0.8H, d, J=3.4 Hz), 4.62 (0.2H, m), 4.95 (0.8H,m), 6.52 (1H, d, J=8.3 Hz), 6.63 (1H, d, J=8.3 Hz), 9.10 (1H, br s). IR(KBr); υ 3230, 1609, 1460, 1317, 1122 cm⁻¹. Mass (FAB); m/z 455((M+H)+). Elementary Analysis: As C₂₇H₃₈N₂O₄.0.5C₄H₆O₆.0.5H₂O; Calcd.:C, 64.66; H, 7.86; N, 5.20. Found.: C, 64.54; H, 7.76; N, 5.31.

Compound 40

mp 210-212° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.25-0.35 (2H,m), 0.45-0.57 (2H, m), 0.84-0.96 (4H, m), 1.11 (1H, m), 1.21-1.35 (8H,m), 1.39-1.580 (4H, m), 1.72 (1H, m), 2.15-2.25 (2H, m), 2.27-2.35 (2H,m), 2.51 (1H, m), 2.65-2.76 (2H, m), 2.79 (0.6H, s), 2.88 (2.4H, S),2.95-3.80 (5H, m), 4.03 (1H, s), 4.34 (0.2H, m), 4.51 (0.8H, d, J=3.4Hz), 4.61 (0.2H, m), 4.89 (0.8H, m), 6.50 (1H, d, J=8.3 Hz), 6.62 (1H,d, J=8,3 Hz), 9.20 (1H, br s). IR (KBr); υ 3180, 1607, 1460, 1359, 1317,1122 cm⁻¹. Mass (FAB); m/z 469 ((M+H)+). Elementary Analysis: AsC₂₈H₄₀N₂O₄.0.5C₄H₆O₆; Calcd.: C, 66.27; H, 7.97; N, 5.15. Found.: C,66.38; H, 8.14; N, 5.33.

Compound 41

mp 195-210° C.; NMR (400 MHz, DMSO-d₆); δ 0.15-0.28 (2H, m), 0.47-0.60(2H, m), 0.92 (1H, m), 1.12 (1H, m), 1.24 (1H, m), 1.40-1.55 (2H, m),1.73 (1H, m), 2.20-2.35 (2H, m), 2.55 (1H, m), 2.60-2.92 (9H, m), 3.05(1H, m), 3.15-3.95 (5.7H, m), 4.10 (1.7H, S), 4.32 (0.2H, m), 4.54(0.8H, d, J=3.4 Hz), 4.61 (0.2H, m), 4.90 (0.8H, m), 6.52 (1H, d, J=8.3Hz), 6.63 (1H, d, J=8.3 Hz), 7.33 (1H, m), 7.71 (1H, mn), 8.40 (1H, m),8.50 (1H, m), 9.08 (1.7H, br s). IR (KBr); υ 3220, 1607, 1460, 1311,1120 cm⁻¹. Mass (FAB); m/z 490 ((M+H)+). Elementary Analysis: AsC₂₉H₃₅N₃O₄.0.85C₄H₆O₆.0.3H₂O; Calcd.: C, 62.50; H, 6.59; N, 6.75.Found.: C, 62.33; H, 6.77; N, 6.78.

Compound 42

mp 254.0-259.0° C. (decomposition, ether); NMR (400 MHz, DMSO-d₆); δ0.40 (1H, m), 0.47 (1H, m), 0.60 (1H, m), 0.69 (1H, m), 1.06 (1H, m),1.40-1.64 (3H, m), 1.90 (1H, m), 2.44 (1H, m), 2.69 (1H, m), 2.85 (3H,s), 2.92 (1H, m), 3.03 (1H, m), 3.09 (1H, dd, J=20.0, 6.4 Hz), 3.23-3.38(3H, m), 3.89 (1H, br d, J=5.4 Hz), 4.59, 4.63, 4.67 (2H, each br s),5.13-5.23 (2H, m), 6.23 (1H, s), 6.58 (1H, d, J=8.1 Hz), 6.71 (1H, d,J=8.1 Hz), 7.35 (1H, m), 7.39, 7.40 (4H, each s), 8.80 (1H, br s), 9.29(1H, br s). IR (KBr); υ 3500, 3100, 2850, 1663, 1470, 1350, 1317, 1156,1120, 1035 cm⁻¹. Mass (FAB); m/z 491 (M+H)+. Elementary Analysis: AsC₂₉H₃₅N₂O₅Cl.0.2H₂O; Calcd.: C, 65.64; H, 6.72; N, 5.28; Cl, 6.68.Found.: C, 65.66; H, 6.71; N, 5.30; Cl, 6.70.

Compound 43

mp 198.0-206.0° C. (decomposition, diethylether); NMR (400 MHz,DMSO-d₆); δ 0.31-0.43 (1H, m), 0.43-0.57 (1H, m), 0.57-0.65 (1H, m),0.65-0.77 (1H, m), 1.00-1.25 (2H, m), 1.38-1.70 (3H, m), 1.87-2.09 (1H,m), 2.35-2.50 (1H, m), 2.60-2.79 (1H, m), 2.89-3.18 (3H, m), 2.87 (1.4H,s), 2.90 (1.6H, s), 3.18-3.38(2H, m), 3.95 (1H, br s), 4.57-4.80 (2H,m), 5.29 (1.2H, S), 5.22-5.40 (0.8H, m), 6.35 (0.6H, brs), 6.45 (0.4H,br S), 6.59 (1H, d, J=7.8 Hz), 6.74 (1H, dd, J=8.3, 2.0 Hz), 7.60-7.74(2H, m), 8.20-8.36 (2H, m), 8.87 (1H, br s), 9.34 (0.4H, s), 9.35 (0.6H,s); IR (KBr); υ 1686, 1638, 1560, 1543, 1522, 1460, 1346, 1120, 1035cm⁻¹. Mass (FAB); m/z 536 ((M+H)+). Elementary Analysis: ASC₂₉H₃₄N₃O₇Cl.0.3H₂O; Calcd.: C, 60.21; H, 6.20; N, 7.26; Cl, 6.13.Found.: C, 60.29; H, 6.18; N, 7.16; Cl, 6.24.

Compound 44

mp>130° C. (decomposition); NMR (400 MHz, DMSo-d₆); δ 0.15-0.30 (2H, m),0.45-0.60 (2H, m), 0.85-0.98 (1H, m), 1.05-1.20 (1H, m), 1.30-1.53 (3H,m), 1.68-1.82 (1H, m), 2.10-2.40 (2H, m), 2.45-2.90 (4H, m), 2.85 (3H,s), 3.00-3.18 (1H, m), 3.21-3.42 (1H, m), 4.11 (2H, s), 4.49-4.62 (2H,m), 5.10-5.30 (2H, m), 6.51 (1H, d, J=8.0 Hz), 6.62 (1H, d, J=8.0 Hz),7.39-7.48 (1H, m), 7.81 (1H, d, J=7.3 Hz), 8.55 (1H, d, J=3.4 Hz), 8.62(1H, s), 9.00 (2H, brs). IR (KBr); υ 3312, 1692, 1603, 1406, 1350, 1311,1267, 1122, 1069, 1035 cm⁻¹; Mass (EI); m/z 492 (M+H)+. ElementaryAnalysis: As C₂₈H₃₃N₃O₅.C₄H₆N₆.0.3H₂O; Calcd.: C, 59.40, H, 6.17; N,6.50. Found.: C, 59.39; H, 6.27; N, 6.52.

Compound 45

mp 197.0° C. (decomposition, diethylether); NMR (400 MHz, DMSO-d₆); δ0.10-0.30 (2H, m), 0.44-0.63 (2H, m), 0.83-0.99 (1H, m), 1.00-1.20 (1H,m), 1.20-1.35 (1H, m), 1.35-1.57 (2H, m), 1.66-1.84 (1H, m), 2.10-2.34(2H, m), 2.39-2.62 (2H, m), 2.62-2.79 (2H, m), 2.82 (0.6H, s), 2.99(2.4H, s), 3.00-3.13 (1H, m), 3.20-3.34 (1H, m), 2.00-3.98 (3H, br s),4.05 (1H, S), 3.95-4.13 (2H, m), 4.41 (0.2H, br d, J=12.2 Hz), 4.52(0.8H, d, J=3.7 Hz), 4.80-4.90 (1H, m), 6.51 (1H, d, J=8.6 Hz), 6.63(1H, d, J=7.9 Hz), 7.15-7.27 (1H, m), 7.27-7.38 (2H, S m), 7.38-7.46(2H, m), 8.65-9.50 (1H, br s); IR (KBr); υ 3430, 1618, 1508, 1460, 1400,1120, 1036, 917, 746, 692 cm⁻¹. Mass (FAB); m/z 507 ((M+H)+). ElementaryAnalysis: As C₃₁H₃₇N₂O₇S.0.5H₂O; Calcd.: C, 63.03; H, 6.48; N, 4.74; S,5.43; Found.: C, 63.14; H, 6.51; N, 4.65; S, 5.33.

Compound 46

mp>230° C. (decomposition); NMR (400 MHz, CD₃OD); δ 0.50 (2H, m), 0.73(1H, m), 0.83 (1H, m), 0.92 (3H, t, J=6.8 Hz), 1.09 (1H, m), 1.28-1.55(8H, m), 1.59-1.79 (4H, m), 1.93 (1H, m), 2.38-2.56 (2H, m), 2.64 (1H,m), 2.84-3.05 (2H, m), 2.93 (0.45H, s), 3.02 (2.55H, s), 3.05-3.22 (2H,m), 3.23-3.40 (2H, m), 3.98 (1H, m), 4.57 (0.15H, m), 4.76 (1H, br d,J=2.9 Hz), 5.09 (0.85H, ddd, J=13.7, 3.9, 3.9 Hz), 6.67 (0.85H, d, J=8.3Hz), 6.68 (0.15H, d, J=8.3 Hz), 6.75 (0.85H, d, J=8.3 Hz), 6.76 (0.15H,d, J=8.3 Hz). IR (KBr); υ 3400, 3158, 1624, 1508, 1468, 1317, 1174,1120, 1038, 907, 808 cm⁻¹. Mass (FAB); m/z 469 ((M+H)+). ElementaryAnalysis: As C₂₈H₄₀N₂O₄.HCl.0.2H₂O; Calcd.: C, 66.11; H, 8.20; N, 5.51;Cl, 6.97. Found.: C, 66.02; H, 8.07; N, 5.64; Cl, 7.02.

Compound 47

mp 169-170° C. (ethylacetate-methanol); NMR (400 MHz, DMSO-d₆); δ 0.18(2H, m), 0.44-0.56 (2H, m), 0.84-0.96 (4H, m), 1.10 (1H, m), 1.30-1.53(5H, m), 1.53-1.62 (2H, m), 1.73 (1H, m), 2.12-2.38 (2H, m), 2.41-2.57(2H, m), 2.63-2.75 (2H, m), 2.80 (3H, s), 3.04 (1H, d, J=18.6 Hz), 3.24(1H, m), 3.45 (3H, br s, 3×OH), 3.95-4.15 (2H, m), 4.04 (1H, s), 4.48(1H, m), 4.56 (1H, m), 6.50 (1H, d, J=7.8 Hz), 6.61 (1H, d, J=7.8 Hz),9.05 (1H, br s, NH+); IR (KBr); υ 3366, 1678, 1613, 1462, 1406, 1350,1317, 1176, 1122, 1069, 1035, 861, 808 cm⁻¹. Mass (FAB); m/z 457((M+H)+). Elementary Analysis: As C₂₆H₃₆N₂O₅.0.5C₄H₆O₆.0.5H₂O; Calcd.:C, 62.21; H, 7.46; N, 5.18. Found.: C, 62.40; H, 7.15; N, 5.23.

Compound 48

mp 200-212° C. (decomposition); NMR (400 MHZ, DMSO-d₆); δ 0.19 (2H, m),0.45-0.57 (2H, m), 0.90 (1H, m), 1.03-1.18 (3H, m), 1.27 (1H, m),1.34-1.63 (8H, m), 1.66-1.82 (4H, m), 2.16-2.56 (6H, m) 2.63-2.77 (2H,m), 2.79 (0.6H, s), 2.89 (2.4H, s), 3.03 (1H, br d, J=18.6 Hz), 3.25(1H, m), 3.45 (3H, br s, 3×OH), 4.03 (1H, s), 4.35 (0.2H, m), 4.52(0.8H, d, J=3.4 Hz), 4.59 (0.2H, m), 4.88 (0.8H, dt, J=14.1, 3.9 Hz),6.50 (1H, d, J=8.3 Hz), 6.62 (0.8H, d, J=8.3 Hz), 6.63 (0.2H, d, J=8.3Hz), 9.06 (1H, br s, NH+). IR (KBr); υ 3316, 1719, 1603, 1462, 1408,1361, 1321, 1172, 1122, 1071, 1038, 917, 808 cm⁻¹. Mass (FAB); m/z 481((M+H) +). Elementary Analysis: As C₂₉H₄₀N₂O₄.0.5C₄H₆O₆.0.2H₂O; Calcd.:C, 66.57; H, 7.82; N, 5.01. Found.: C, 66.63; H, 7.83; N, 5.06.

Compound 49

mp>132° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.20 (2H, m),0.48-0.58 (2H, m), 0.91 (1H, m), 1.10 (1H, m), 1.22-1.54 (3HI, m), 1.73(1H, m), 2.06-2.34 (2H, m), 2.45-2.62 (2H, m), 2.65-2.78 (2H, m), 2.81(3H, s), 3.06 (1H, br d, J=18.6 Hz), 3.27 (1H, m), 3.29 (3H, br s), 3.50(3.2H, br s, 3.1×OH+0.1×COOH), 3.52-3.59 (2H, m), 4.06 (1.lH, s),4.07-4.30 (2H, m), 4.40-4.64 (2H, m), 6.51 (1H, d, J=8.0 Hz), 6.62 (1H,d, J=8.0 Hz), 9.06 (1H, brs, NH+). IR (KBr); υ 3342, 1686, 1609, 1462,1406, 1346, 1317, 1249, 1176, 1120, 1069, 1036, 924, 903, 806 cm⁻. Mass(FAB); m/z 459 ((M+H)+). Elementary Analysis: AsC₂₅H₃₄N₂O₆.0.55C₄H₆O₆.0.9H₂O; Calcd.: C, 58.62; H, 7.07; N, 5.03.Found.: C, 58.67; H, 7.06; N, 4.91.

Compound 50

mp 260.0° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.08-0.32 (2H,m), 0.40-0.64 (2H, m), 0.80-1.00 (1H, m), 1.00-1.38 (7H, m), 1.38-1.83(6H, m), 2.05-2.38 (3H, m), 2.40-2.65 (2H, m), 2.65-2.81 (3H, m), 2.83(0.9H, s), 2.95 (2.1H, s), 2.98-3.15 (1H, m), 3.15-3.44 (1H, m), 4.47(0.3H, m), 4.56 (0.3H, m), 4.58 (0.7H, d, J=3.4 Hz), 4.90 (0.7H, m),3.50-6.20 (5H, br s), 6.29 (0.3H, d, J=15.1 Hz), 6.37 (0.7H, d, J=14.7Hz), 6.51 (1H, d, J=8.3 Hz), 6.57-6.74 (2H, m); IR (KBr); υ 3420, 1651,1599, 1450, 1408, 1321, 1120, 1036, 922, 441 cm⁻. Mass (FAB); m/z 493((M+H)+). Elementary Analysis: As C₃₀H₄₃N₂O₈P1.1.3H₂O; Calcd.: C, 58.68;H, 7.48; N, 4.56; P, 5.04. Found.: C, 58.60; H, 7.44; N, 4.61; P, 5.12.

Embodiments 41-44

17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-isobutyl-3,4-dichlorophenylacetoamido)morphinan.hydrochloride 51 (yield: 78%),17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(3,4-dichlorophenylacetoamid)morphinanhydrochloride 52 (yield: 92%),17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methyl-3,4-dichlorophenylacetoamido)morphinan.hydrochloride53 (yield: 51%), and17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-ethyl-3,4-dichlorophenylacetoamido)morphinane.hydrochloride 54 (yield: 56%) were obtained by following theprocedure of example 11 but using17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-isobutylaminomorphinan5, 17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-aminomorphinan (J.B. Jiang, R. N. Hanson, P. S. Portoghese, and A. E. Takemori, J. Med.Chem., 20, 1100 (1977).),17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-methylaminomorphinan10, and17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-ethylaminomorphinan11 instead of the starting material17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan4.

Compound 51

mp 185-188° C.; NMR (400 MHz, DMSO-d₆); δ 0.40 (1H, m), 0.48 (1H, m),0.61 (1H, m), 0.72 (4H, m), 0.88 (4H, m), 1.06 (2H, m), 1.57 (3H, m),1.90 (2H, m), 2.42 (1H, m), 2.68 (1H, m), 3.00 (3H, m), 3.36 (2H, m),3.45 (1H, m), 3.86 (3H, m), 4.4-5.1 (2H, m), 6.19 (0.7H, s), 6.50 (0.3H,s), 6.58 (1H, m), 6.73 (1H, d, J=7.8 Hz), 7.27 (1H, m), 7.52 (1H, d,J=4.4 Hz), 7.59 (1H, t, J=8.3 Hz), 8.82 (1H, brs), 9.26 (0.7H, s), 9.30(0.3H, s); IR (KBr); υ 3370, 1620, 1510, 1468, 1120, 1035 cm⁻¹. Mass(FAB); m/z 585 (M+H); Elementary Analysis: As C₃₂H₃₈N₂O₄Cl₂.HCl.0.2H₂O;Calcd.: C, 61.43; H, 6.35; N, 4.48; Cl, 17.00. Found.: C, 61.44; H,6.42; N, 4.45; Cl, 16.82.

Compound 52

mp 212.0-215.0° C. (decomposition, ether); NMR (400 MHz, DMSO-d₆); δ0.39 (1H, m), 0.47 (1H, m), 0.60 (1H, m), 0.68 (1H, m), 0.97 (tH, m),1.05 (1H, m), 1.40 (2H, dd, J=14.7, 9.8 Hz), 1.60 (1H, d, J=10.7 Hz),1.84 (1H, dt, J=15.1, 9.3 Hz), 2.44 (1H, dt, J=13.2, 4.9 Hz), 2.70 (1H,br q, J=12.7 Hz), 2.94 (1H, m), 3.04 (2H, dd, J=19.5, 6.8 Hz), 3.25-3.35(2H, m), 3.55 (2H, s), 3.89 (1H, d, J=6.8 Hz), 4.38 (1H, m), 4.59 (1H,d, J=3.4 Hz), 6.25 (1H, s), 6.56 (1H, d, J=8.3 Hz), 6.73 (1H, d, J=8.3Hz), 7.29 (1H, dd, J=8.3, 2.0 Hz), 7.56 (1H, d, J=2.0 Hz), 7.57 (1H, d,J=8.3 Hz), 8.14 (1H, d, J=8.3 Hz), 8.83 (1H, br s), 9.28 (1H, s). IR(KBr); υ 3400, 2942, 1651, 1510, 1460, 1236, 1120, 1035, 903, 787 cm¹.Mass (FAB); m/z 529 (M+H)+. Elementary Analysis: AsC₂₈H₃₁N₂O₄Cl₃.0.3H₂O; Calcd.: C, 58.86; H. 5.58; N, 4.90; Cl, 18.62.Found.: C, 58.99; H, 5.79; N, 4.93; Cl, 18.61.

Compound 53

mp 194-196° C. (decomposition); NMR (400 MHz, CDCl₃+D20, Data for freebase); δ 0.09-0.17 (2H, m), 0.49-0.57 (2H, m), 0.78-0.89 (2H, m), 1.05(0.7H, dt, J=13.2, 3.4 Hz), 1.42-1.51 (0.3H, m), 1.49 (2H, brd, J=13.2Hz), 1.97-2.29 (3H, m), 2.36 (2H, d, J=6.4 Hz), 2.56-2.69 (2H, m), 2.92(2.1H, s), 2.99 (0.9H, s), 3.00-3.08 (2H, m), 3.48 (0.7H, d, J=15.6 Hz),3.49-3.56 (1H, m), 3.66 (0.7H, d, J=15.6 Hz), 3.70 (0.6H, s), 4.55(0.3H, d, J=8.3 Hz), 4.58 (0.7H, d, J=8.3 Hz), 6.57 (0.3H, d, J=8.3 Hz),6.73 (0.3H, d, J=8.3 Hz), 6.78-6.82 (1.4H, m), 6.83 (0.7H, d, J=8.3 Hz),7.11 (0.3H, dd, J=8.3, 2.5 Hz), 7.23 (0.7H, d, J=8.3 Hz), 7.36 (0.3H, d,J=2.0 Hz), 7.39 (0.3H, d, J=8.3 Hz). IR (KKBr); υ 3420, 1620, 1321,1127, 1035 cm⁻¹. Mass (FAB); m/z 543 (M+H)+. Elementary Analysis: AsC₂₉H₃₂N₂O₄Cl₂.HCl.0.7H₂O; Calcd.: C, 58.78; H, 5.85; N, 4.73; Cl, 17.95.Found.: C, 58.72; H, 5.86; N, 4.71; Cl, 18.03.

Compound 54

mp 184-187° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.35-0.75 (4H,m), 1.00-1.53 (4H, m), 1.09 (2.25H, t, J=6.8 Hz), 1.15 (0.75H, t, J=6.8Hz), 1.60-1.75 (1H, m), 1.93-2.10 (1H, m), 2.38-2.50 (1H, m), 2.80-2.93(1H, m), 2.96-3.08 (2H, m), 3.15-3.35 (3H, m), 3.40-3.60 (2H, m), 3.56(2.25H, s), 3.76 (0.75H, s), 3.76-3.87 (1H, m), 4.76 (0.75H, brd, J=7.9Hz), 5.07 (0.25H, brd, J=7.9 Hz), 6.08 (0.25H, brs), 6.45 (0.75H, brs),6.63 (0.25H, d, J=7.9 Hz), 6.71 (0.25H, d, J=7.9 Hz), 6.72 (0.75H, d,J=8.1 Hz), 6.80 (0.75 H, d, J=8.1 Hz), 6.98 (0.75H, dd, J=8.3, 2.0 Hz),7.03 (0.75H, d, J=2.0 Hz), 7.24 (0.25H, dd, J=8.3, 2.0 Hz), 7.51 (0.75H,d, J=8.3 Hz), 7.53 (0.25H, d, J=2.0 Hz), 7.57 (0.25H, d, J=8.3 Hz), 8.80(1H, brs) 9.31 (0.25H, s), 9.65 (0.75H, s). IR (KBr); υ 3420, 1626,1508, 1319, 1127, 1033 cm⁻¹. Mass (FAB); m/z 557 (M+H)+. ElementaryAnalysis: As C₃₀H₃₄N₂O₄Cl₂.HCl.0.3H₂O; Calcd.: C, 60.12; H, 5.99; N,4.67; Cl, 17.74. Found.: C, 60.14; H, 6.17; N, 4.70; Cl, 17.70.

Examples 45-63

17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methylphenylacetamido)morphinanhydrochloride55 (yield: 57%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methylbenzyloxycarbamido)morphinanehydrochloride56 (yield: 43%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-phenylpropionamido)morphinan. hydrochloride 57 (yield: 84%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methylphenoxyacetamido)morphinan.tartrate58 (yield: 75%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methylbutyroxycarbamido)morphinan.tartrate59 (yield: 81%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan.tartrate60 (yield: 84%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-60-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan.tartrate 61 (yield: 91%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methylhexanamido)morphinan.tartrate 62 (yield: 43%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-methoxycinnamamido)morphinan.tartrate 63 (yield: 88%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-cyclopentylpropionamido)morphinan.tartrate64 (yield: 39%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methylthiophenoxyacetamido)morphinan.tartrate65 (yield: 75%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-2-naphthamido)morphinan.hydrochloride66 (yield: 95%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-2-methoxyethoxycarbamido)morphinan.tartrate67 (yield: 63%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6,-(N-methyl-3-cyclohexylacrylamido)morphinan.tartrate 68 (yield: 77%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-methylcinnamamido)morphinan.hydrochloride69 (yield: 87%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-trans-3-(2-furyl)acrylamido]morphinan.hydrochloride 70 (yield: 80%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-trans-3-(3-thienyl)acrylamido]morphinan.methanesulfonate 71 (yield: 88%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-2-trifluoromethylcinnamamido)morphinan.hydrochloride72 (yield: 93%), and17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-4-triflqoromethylcinnamamido)morphinan.tartrate 73 (yield: 84%) were obtained by following theprocedure of example 11 but using17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-methylaminomorphinan10 instead of the starting material17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan4, and using phenylacetyl chloride, benzyl chloroformate,3-phenylpropionyl chloride, phenoxyacetyl chloride, butyl chloroformate,3-trifluoromethylcinnamoyl chloride, trans-3-(3-furyl)acryloyl chloride,hexanoyl chloride, 3-methoxycinnamoyl chloride, 3-cyclopentylpropionylchloride, thiophenoxyacetyl chloride, 2-naphthoyl chloride,2-methoxyethyl chloroformate, trans-3-cyclohexylacryloyl chloride,3-methylcinnamoyl chloride, trans-3-(2-furyl)acryloyl chloride,trans-3-(3-thienyl)acryloyl chloride, 2-trifluoromethylcinnamoylchloride and 4-trifluoromethylcinnamoyl chloride instead of3,4-dichlorophenylacetyl chloride.

Compound 55

mp 205-207° C.; NMR (500 MHz, DMSO-d₆); δ 0.40 (1H, m), 0.50 (1H, m),0.57 (1H, m), 0.67 (1H, m), 0.81 (1H, m), 1.00-1.08 (2H, m), 1.37-1.56(2H, m), 1.97 (1H, m), 2.42-2.53 (2H, m), 2.83 (3H, s), 2.85 (1H, m),2.45-3.07 (3H, m), 3.25-3,37 (2H, m), 3.46-3.57 (2H, m), 3.81 (0.8H, m),4.04 (0.2H, m), 4.81 (0.8H, m), 4.88 (0.2H, m), 6.31 (0.2H, br S), 6.42(0.8H, br s), 6.63 (0.2H, d, J=8.1 Hz), 6.70 (0.2H, d, J=8.1 Hz), 6.75(0.8H, d, J=8.1 Hz), 6.77-6.80 (1.4H, m), 6.84 (0.8H, d, J=8.1 Hz),7.12-7.33 (3.6H, m), 8.80 (1H, br s), 9.27 (0.2H, s), 9.65 (0.8H, s); IR(KBr); υ 3400, 1620, 1502, 1460, 1321, 1125, 1033, 920, 859, 748, 719cm⁻¹; Mass (FAB); m/z 475 ((M+H)+). Elementary Analysis: AsC₂₉H₃₄N₂O₄.HCl.0.5H₂O; Calcd.: C, 66.98; H, 6.98; N, 5.38; Cl, 6.82.Found.: C, 67.25; H, 7.05; N, 5.40; Cl, 6.43.

Compound 56

mp 189.0-192.0° C. (decomposition, diethylether); NMR (400 MHz,DMSO-d₆); δ 0.31-0.47 (1H, m), 0.47-0.56 (1H, m), 0.56-0.63 (1H, m),0.63-0.76 (1H, m), 1.00-1.14 (1H, m), 1.20-1.52 (3H, m), 1.63-1.82 (1H,m), 2.03-2.22 (1H, m), 2.34-2.59 (1H, m), 2.80-2.90 (1H, m), 2.90 (1.7H,s), 2.93 (1.3H, s), 2.98-3.17 (2H, m), 3.22-3.40 (2H, m), 3.60-3.72(0.6H, m), 3.72-3.80 (0.4H, m), 3.84 (1H, d, J=4.9 Hz), 4.83 (1H, brt),4.98 (0.4H, d, J=13.2 Hz), 5.04 (1H, d, J=12.7 Hz), 5.09 (0.6H, d,J=13.2 Hz), 6.42 (1H, brs), 6.72 (0.6H, d, J=8.3 Hz), 6.77 (0.4H, d,J=7.8 Hz), 7.37 (5H, s), 7.16-7.45 (2H, m), 8.83 (1H, brs), 9.32 (0.4H,s), 9.45 (0.6H, s); IR (KBr); υ 1678, 1560, 1543, 1460, 1315, 1152, 1033cm⁻¹. Mass (FAB); m/z 491 ((M+H)+). Elementary Analysis: AsC₂₉H₃₅N₂O₅Cl; Calcd.: C, 66.09; H, 6.69; N, 5.31; Cl, 6.73; Found.: C,66.10; H, 6.64; N, 5.18; Cl, 6.56.

Compound 57

mp 207.0° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.31-0.47 (1H,m), 0,47-0.55 (1H, m), 0.55-0.63 (1H, m), 0.63-0.75 (1H, m), 0.99-1.13(1H, m), 1.13-1.50 (3H, m), 1.60-1.78 (1H, m), 1.98-2.16 (1H, m),2.28-2.52 (3H, m), 2.52-2.95 (4H, m), 2.83 (2.4H, s), 2.96 (0.6H, s),2.95-3,16 (2H, m), 3.22-3.35 (2H, m), 3.36-3.53 (1H, m), 3.83 (1H, m),4.79 (0.8H, d, J=7.8 Hz), 4.85 (0.2H, d, J=8.3 Hz), 6.38 (0.2H, m), 6.46(0.8H, m), 6.60-6.80 (2H, m), 7.02-7.32 (5H, m), 8.82 (1H, br s), 9.29(0.2H, s), 9.56 (0.8H, s); IR (KBr); υ 3416, 1622, 1502, 1454, 1410,1383, 1321, 1125 cm⁻¹. Mass (FAB); m/z 489 (M+; Elementary Analysis: AsC₃₀H₃₇N₂O₄Cl₁.0.2H₂O; Calcd.: C, 67.92; H, 7.11; N, 5.28; Cl, 6.68;Found.: C, 67.96; H, 7.06; N, 5.27; Cl, 6.85.

Compound 58

mp 150-200° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.21 (2H, m),0.46-0.58 (2H, m), 0.90 (1H, m), 1.15-1.46 (3H, m), 1.57 (1H, m),2.03-2.17 (2H, m), 2.28 (1H, m), 2.58-2.78 (3H, m), 2.82 (2.4H, s), 3.00(0.6H, s), 3.08 (1H, d, J=18.9 Hz), 3.24 (1H, m), 3.45 (1H, m), 3.50(3H, br s, 3×OH), 4.00-4.05 (1H, m), 4.04 (1H, s), 4.63-4.82 (3H, m),6.54-6.67 (2H, m), 6.78-6.95 (3H, m), 7.18-7.29 (2H, m), 9.34 (1H, br s,NH+). IR (KBr); υ 3390, 1638, 1601, 1497, 1323, 1241, 1118, 1064, 1035,922, 859 cm⁻¹. Mass (FAB); m/z 491 ((M+H)+). Elementary Analysis: AsC₂₉H₃₄N₂O₅.0.5C₄H₆O₆.1.1H₂O; Calcd.: C, 63.60; H, 6.75; N, 4.78. Found.:C, 63.69; H, 6.63; N, 4.72.

Compound 59

mp 110-150° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.20 (2H, m),0.45-0.56 (2H, m), 0.76-0.96 (4H, m), 1.14-1.40 (5H, m), 1.40-1.60 (3H,m), 2.01-2.15 (2H, m), 2.25 (1H, m), 2.55-2.77 (3H, m), 2.82 (3H, s),3.06 (1H, d, J=18.6 Hz), 3.23 (1H, m), 3.53 (3H, br s, 3×OH), 3.53-3.68(2H, m), 3.84-3.98 (2H, m), 4.01 (1H, s), 4.67 (1H, m), 6.55 (1H, d,J=8.1 Hz), 6.61 (1H, d, J=8.1 Hz), 9.10 (1H, br s, NH+); IR (KBr); υ3420, 1678, 1607, 1460, 1408, 1359, 1315, 1164, 1122, 1067, 1035, 922,861 cm⁻¹. Mass (FAB); m/z 457 ((M+H)+). Elementary Analysis: AsC₂₆H₃₆N₂O₅.0.5C₄H₆O₆.0.5H₂O; Calcd.: C, 62.21; H, 7.46; N, 5.18. Found.:C, 62.21; H, 7.59; N, 5.33.

Compound 60

mp 156-159° C.; NMR (400 MHz, DMSO-d₆); δ 0.21 (2H, m), 0.52 (2H, m),0.91 (1H, m), 1.2-1.5 (3H, m), 1.57 (1H, d, J=13.2 Hz), 2.12 (2H, m),2.29 (1H, m), 2.49 (1H, m), 2.6-2.8 (3H, m), 2.90 (2H, s), 3.08 (1H, d,J=18.6 Hz), 3.17 (1H, s), 3.26 (1H, m), 3.67 (0.7H, m), 4.02 (1H, S),4.21 (0.3H, m), 4.68 (0.7H, d, J=7.8 Hz), 4.79 (0.3H, d, J=8.3 Hz),6.6-6.8 (2.6H, m), 7.37 (1H, dd, J=7.3, 16.1 Hz), 7.5-7.8 (3.8H, m),8.02 (0.3H, d, J=7.8 Hz), 8.14 (0.3H, s); IR (KBr); υ 3350, 1649, 1601,1336, 1168, 1127 cm⁻¹; Mass (FAB); m/z 555 (M+H); Elementary Analysis:As C₃₁H₃₃N₂O₄F₃.0.5(C₄H₆O₆).0.3H₂O; Calcd.: C, 62.41; H, 5.81; N, 4.41;F, 8.98; Found.: C, 62.32; H, 5.99; N, 4.48; F, 8.88.

Compound 61

mp 168-172° C.; NMR (400 MHz, DMSo-d₆); δ 0.20 (2H, brs), 0.52 (2H, m),0.90 (1H, m), 1.2-1.4 (3H, m), 1.56 (1H, d, J=13.2 Hz), 2.12 (2H, rm),2.24 (1H, m), 2.47 (1H, m), 2.5-2.8 (3H, m), 2.86 (2H, s), 3.08 (1H, d,J=19.6 Hz), 3.10 (1H, s), 3.22 (1H, m), 3.60 (0.7H, m), 4.00 (1H, s),4.19 (0.3H, m), 4.66 (0.7H, d, J=8.3 Hz), 4.76 (0.3H, d, J=8.3 Hz), 6.39(0.7H, d, J=15.6 Hz), 6.5-6.7 (2H, m), 6.74 (0.7H, d, J=8.3 Hz), 6.89(0.3H, d, J=15.1 Hz), 7.00 (0.3H, s), 7.21 (0.7H, d, J=15.6 Hz), 7.36(0.3H, d, J=15.1 Hz), 7.66 (0.7H, s), 7.72 (0.311, s), 7.92 (0.7H, s),8.03 (0.3H, s); IR (KBr); υ 3370, 1651, 1599, 1323, 1158, 1114 cm⁻¹;Mass (FAB); m/z 477 (M+H); Elementary Analysis: AsC₂₈H₃₂N₂O₅.0.5(C₄H₆O₆).0.2H₂O; Calcd.: C, 64.90; H, 6.43; N, 5.04.Found.: C, 64.79; H, 6.59; N, 5.01.

Compound 62

mp 150-158° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.23 (2H, m),0.48-0.59 (2H, m), 0.79 (2.1H, br t, J=6.8 Hz), 0.88 (0.9H, br t, J=6.8Hz), 0.92 (1H, m), 1.11-1.22 (3H, m), 1.23-1.51 (6H, m), 1.58 (1H, m),1.98-2.33 (5H, m), 2.52 (1H, m), 2.67-2.82 (3H, m), 2.77 (2.1H, s), 2.93(0.9H, s), 3.11 (1H, br d, J=19.1 Hz), 3.33 (1H, m), 3.48 (1H, m), 3.50(5H, br s, 5×OH), 4.08 (2H, s), 4.60 (0.7H, d, J=8.3 Hz), 4.72 (0.3H, d,J=8.3 Hz), 6.56 (0.3H, d, J=7.8 Hz), 6.60 (0.7H, d, J=7.8 Hz), 6.62(0.3H, d, J=7.8 Hz), 6.67 (0.7H, d, J=7.8 Hz), 9.26 (1H, br s, NH+). IR(KBr); υ 3314, 1719, 1618, 1460, 1412, 1311, 1267, 1120, 1069, 1035,922, 859 cm⁻¹. Mass (FAB); m/z 455 ((M+H)+). Elementary Analysis: AsC₂₇H₃₈N₂O₄.C₄H₆O₆.1.0H₂O; Calcd.: C, 59.79; H, 7.45; N, 4.50. Found.: C,59.59; H, 7.46; N, 4.67.

Compound 63

mp 160° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.15-0.35 (2H,mn), 0.45-0.65 (2H, m), 0.85-1.05 (1H, m), 1.20-1.50 (3H, m), 1.52-1.70(1H, m), 2.00-2.25 (2H, m), 2.25-2.42 (1H, m), 2.63-2.77 (3H, m), 2.90(1.8H, s), 2.90-4.20 (3H, br s), 3.05-3.22 (1H, m), 3.15 (1.2H, s),3.22-3.42 (1H, m), 3.50-3.74 (1.6H, m), 3.77 (1.8H, s), 3.80 (1.2H, s),4.00 (1H, s), 4.20 (0.4H, br s), 4.71 (0.6H, d, J=7.8 Hz), 4.80 (0.4H,d, J=8.3 Hz), 6.55-6.71 (2.6H, m), 6.92 (0.6H, dd, J=8.3, 2.5 Hz),6.95-7.03 (1H, m), 7.10 (0.6H, d, J=7.3 Hz), 7.17 (0.4H, d, J=15.1 Hz),7.23-7.35 (2.4H, m), 7.42 (0.4H, d, J=15.6 Hz), 9.07 (0.4H, br s), 9.37(0.6H, br s); IR (KBr); υ 3390, 1642, 1599, 1460, 1408, 1313, 1272,1127, 1035, 787, 683 cm⁻¹. Mass (FAB); m/z 517 ((M+H) +); ElementaryAnalysis: As C₃₃H₃₉N₂O₈.0.7H₂O; Calcd.: C, 65.59; H, 6.74; N, 4.64;Found.: C, 65.46; H, 6.78; N, 4.70.

Compound 64

mp 145-160° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.23 (2H, m),0.48-0.59 (2H, m), 0.82-1.12 (3H, m), 1.14-1.78 (13H, m), 2.00-2.33 (5H,m), 2.52 (1H, m), 2.66-2.81 (3H, m), 2.76 (2.4H, s), 2.93 (0.6H, s),3.11 (1H, br d, J=18.6 Hz), 3.31 (1H, m), 3.46 (1H, m), 3.50 (5H, br s,5×OH), 4.07 (2H, s), 4.61 (0.8H, d, J=7.8 Hz), 4.71 (0.2H, d, J=7.8 Hz),6.56 (0.2H, d, J=8.0 Hz), 6.59 (0.8H, d, J=8.0 Hz), 6.61 (0.2H, d, J=8.0Hz), 6.66 (0.8H, d, J=8.0 Hz), 9.25 (1H, br s, NH+). IR (KBr); υ 3398,1721, 1620, 1456, 1408, 1325, 1243, 1125, 1071, 1035, 922, 859 cm¹. Mass(FAB); m/z 481 ((M+H)+). Elementary Analysis: AsC₂₉H₄₀N₂O₄.C₄H₆O₆.0.3H₂O; Calcd.: C, 62.31; H, 7.38; N, 4.40. Found.: C,62.18; H, 7.65; N, 4.57.

Compound 65

mp 145.0° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.15-0.30 (2H,m), 0.43-0.60 (2H, m), 0.83-0.98 (1H, m), 1.13-1.26 (1H, m), 1.26-1.41(2H, m), 1.43-1.62 (1H, m), 1.97-2.19 (2H, m), 2.19-2.33 (1H, m),2.40-2.55 (1H, m), 2.55-2.78 (3H, m), 2.80 (2.4H, s), 3.03 (0.6H, s),3.05 (1H, br d, J=13.4 Hz), 3.22 (1H, br s), 2.90-4.30 (3H, br s),3.42-3.52 (1H, m), 3.74 (0.8H, d, J=14.0 Hz), 3.91 (0.8H, d, J=14.7 Hz),3.96 (0.2H, d, J=14.6 Hz), 4.02 (0.2H, d, J=14.6 Hz), 4.04 (1H, s), 4.61(0.8H, d, J=7.9 Hz), 4.73 (0.2H, d, J=7.9 Hz), 6.55 (0.2H, d, J=7.9 Hz),6.59-6.67 (1H, m), 6.71 (0.8H, d, J=7.9 Hz), 7.08-7.26 (4.2H, m), 7.30(0.4H, t), 7.35-7.42 (0.4H, m), 9.10-9.60 (1H, br s); IR (KBr); υ 3380,1620, 1508, 1408, 1313, 1267, 1122, 1035, 690 cm⁻¹. Mass (FAB); m/z 507((M+H)+). Elementary Analysis: As C_(31.4)H37.6N₂O_(7.6)S1.0.6H₂O;Calcd.: C, 62.08; H, 6.44; N, 4.61; S, 5.28. Found.: C, 61.84; H, 6.60;N, 4.67; S, 5.35.

Compound 66

mp 220° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.34 (1H, m), 0.47(1H, m), 0.54 (1H, m), 0.62 (1H, m), 0.87 (1H, m), 0.99 (1H, m), 1.28(1H, nm), 1.4-1.6 (2H, m), 2.17 (1H, m), 2.34 (1H, m), 2.52 (1H, m),2.7-2.9 (2H, m), 3.01 (1H, m), 3.10 (2H, s), 3.2-3.4 (3.7H, m), 3.70(0.7H, m), 3.87 (0.3H, m), 4.15 (0.3H, m), 5.00 (0.7H, d, J=7.8 Hz),5.06 (0.3H, m), 6.37 (0.3H, m), 6.39 (0.7H, d, J=7.8 Hz), 6.58 (0.7H, d,J=8.3 Hz), 6.71 (0.3H, m), 7.6-8.0 (7H, m); IR (KBr); υ 3400, 1620,1319, 1176, 1120, 1035 cm⁻¹. Mass (FAB); m/z 511 (M+H); ElementaryAnalysis: As C₃₂H₃₄N₂O₄.HCl.0.4H₂O; Calcd.: C, 69.34; H, 6.51; N, 5.05;Cl, 6.40; Found.: C, 69.13; H, 6.86; N, 4.96; Cl, 6.73.

Compound 67

mp >130° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.23 (2H, m),0.48-0.58 (2H, m), 0.92 (1H, m), 1.23-1.38 (3H, m), 1.58 (1H, m),2.02-2.18 (2H, m), 2.27 (1H, m), 2.52 (1H, m), 2.66-2.79 (3H, m),2.81-2.87 (3H, m), 3.08 (1H, br d, J=18.6 Hz), 3.14 (1.5H, br s), 3,28(1.5H, br s), 3.30 (1H, m), 3.42-3.57 (2H, m), 3.50 (4H, br s,3.5×OH+0.5×COOH), 3.61 (1H, m), 4.02-4.13 (2H, m), 4.05 (1.5H, s), 4.69(1H, m), 6.56 (1H, d, J=8.3 Hz), 6.63 (1H, m), 9.15 (1H, br s, NH+). IR(KBr); υ 3424, 1686, 1609, 1460, 1410, 1313, 1251, 1123, 1066, 1033,922, 905, 859 cm⁻¹. Mass (FAB); m/z 459 ((M+H)+). Elementary Analysis:As C₂₅H₃₄N₂O₆.0.75C₄H₆O₆.0.8H₂O; Calcd.: C, 57.44; H, 6.90; N, 4.78.Found.: C, 57.41; H, 6.89; N, 4.71.

Compound 68

mp 154.0° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.16-0.32 (2H,m), 0.42-0.62 (2H, m), 0.82-1.02 (2H, m), 1.02-1.42 (7H, m), 1.42-1.80(6H, m), 1.88-2.33 (4H, m), 2.42-2.58 (1H, m), 2.58-2.87 (3H, m),2.60-5.10 (3H, br S), 2.81 (2.IH, s), 3.01 (0.9H, s), 3.09 (1H, br d,J=18.3 Hz), 3.28 (1H, br s), 3.60 (0.7H, m), 4.05 (1H, s), 4.11 (0.3H,m), 4.61 (0.7H, d, J=7.9 Hz), 4.73 (0.3H, d, J=8.5 Hz), 5.93 (0.7H, d,J=15.3 Hz), 6.33 (0.7H, d, J=15.3 Hz), 6.34 (0.3H, d, J=15.3 Hz),6.52-6.62 (1.6H, m), 6.66 (0.7H, d, J=8.5 Hz), 8.60-9.60 (1H, br s); IR(KBr); υ 3322, 1651, 1601, 1504, 1450, 1410, 1311, 1267, 1216, 1129, 681cm⁻¹. Mass (FAB); m/z 493 ((M+H)+). Elementary Analysis: AsC_(32.8)H_(44.2)N₂O_(8.2).0.8H₂O; Calcd.: C, 64.36; H, 7.54; N, 4.58;Found.: C, 64.37; H, 7.67; N, 4.58.

Compound 69

mp 245° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.42 (1H, m), 0.50(1H, m), 0.59 (1H, m), 0.69 (1H, m), 1.07 (1H, m), 1.2-1.5 (3H, m), 1.72(1H, d, J=13.7), 2.12 (1H, m), 2.34 (3H, s), 2.4-2.6 (2H, m), 2.88 (1H,m), 2.92 (2H, s), 3.0-3.1 (2H, m), 3.18 (1H, s), 3.3-3.4 (2H, m), 3.66(0.7H, m), 3.83 (1H, m), 4.20 (0.3H, m), 4.83 (0.7H, d, J=7.8 Hz), 4.90(0.3H, d, J=8.3 Hz), 6.6-6.8 (2H, m), 6.85 (0.7H, d, J=8.3 Hz), 7.1-7.3(4.4H, m), 7.41 (0.3H, d, J=15.1 HZ), 7.48 (0.3H, d, J=7.3 Hz), 7.54(0.3H, brs); IR (KBr); υ 3390, 1647, 1605, 1323, 1127, 1035 cm⁻¹. Mass(FAB); m/z 501 (M+H); Elementary Analysis: As C₃₁H₃₆N₂O₄.HCl.0.8H₂O;Calcd.: C, 67.51; H, 7.06; N, 5.08; Cl, 6.43. Found.: C, 67.35; H, 7.05;N, 5.17; Cl, 6.53.

Compound 70

mp 200° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.42 (1H, m), 0.53(1H, m), 0.61 (LH, m), 0.69 (1H, m), 1.08 (1H, m), 1.28 (0.5H, m),1.3-1.5 (2.5H, m), 1.74 (1H, m), 2.15 (1H, m), 2.4-2.6 (2.5H, m),2.8-2.9 (1.5H, m), 2.93 (1.5H, s), 3.0-3.1 (2H, m), 3.16 (1.5H, s),3.3-3.4 (2H, m), 3.61 (0.5H, m), 3.85 (1H, brs), 4.20 (0.5H, m), 4.85(0.5H, d, J=7.3 Hz), 4.91 (0.5H, d, J=7.8 Hz), 6.4-6.7 (3.5H, m),6.8-6.9 (1.5H, m),7.14 (0.5H, d, J=15.1 Hz), 7.28 (0.5H, d, J=15.6 Hz),7.68 (0.5H, s), 7.80 (0.5H, s); IR (KBr); υ 3390, 1647, 1597, 1321,1127, 1017 cm⁻¹. Mass (FAB); m/z 477 (M+H); Elementary Analysis: AsC₂₈H₃₂N₂O₅.HCl.0.6H₂O; Calcd.: C, 64.20; H, 6.58; N, 5.35; Cl, 6.77.Found.: C, 64.21; H, 6.84; N, 5.38; Cl, 6.69.

Compound 71

mp 235° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.42 (1H, m), 0.51(1H, m), 0.60 (1H, m), 0.68 (1H, m), 1.08 (1H, m), 1.2-1.5 (3H, m), 1.72(1H, d, J=12.2 Hz), 2.12 (1H, m), 2.34 (3H, s), 2.4-2.5 (2H, m), 2.86(1H, m), 2.91 (2H, s), 3.0-3.1 (2H, m), 3.15 (1H, s), 3.3-3.5 (2H, m),3.61 (0.7H, m), 3.82 (1H, brs), 4.19 (0.3H, m), 4.81 (0.7H, d, J=7.8Hz), 4.89 (0.3H, d, J=8.3 Hz), 6.46 (0.7H, d, J=15.6 Hz), 6.6-6.7 (1.3H,m), 6.85 (0.7H, d, J=7.8 Hz), 7.00 (0.3H, d, J=15.1 Hz), 7.26 (0.7H, d,J=4.9 Hz), 7.31 (0.7H, d, J=15.6 Hz), 7.46 (0.3H, d, J=15.1 Hz), 7.5-7.7(2H, m), 7.87 (0.3H, s); IR (KBr); υ 3410, 1642, 1595, 1323, 1127, 1035,859 cm⁻¹. Mass (FAB); m/z 493 (M+H); Elementary Analysis: AsC₂₈H₃₂N₂O₄S.CH₃SO₃H.0.2H₂O; Calcd.: C, 58.80; H, 6.19; N, 4.73; S,10.83; Found.: C, 58.60; H, 6.42; N, 4.72; S, 10.82.

Compound 72

mp 196-199° C.; NMR (400 MHz, DMSO-d₆); δ 0.41 (1H, m), 0,53 (1H, m),0.59 (1H, m), 0.67 (1H, m), 1.09 (1H, m), 1.3-1.5 (3H, m), 1.73 (1H, d,J=13.2 Hz), 2.20 (1H, m), 2.4-2.6 (2H, m), 2.88 (1H, m), 2.97 (2H, s),3.0-3.1 (2H, m), 3.23 (1H, s), 3.3-3.4 (2H, m), 3.68 (0.7H, m), 3.87(1H, brs), 4.18 (0.3H, m), 4.88 (0.7H, d, J=7.8 Hz), 4.97 (0.3H, d,J=8.3 Hz), 6.6-6.9 (2.7H, m), 7.28 (0.3H, d, J=15.1 Hz), 7.5-7.7 (1.7H,m), 7.7-7.9 (3H, m), 8.14 (0.3H, d, J=7.8 Hz); IR (KBr); υ 3400, 1649,1605, 1460, 1317, 1125, 1036 cm⁻¹. Mass (FAB); m/z 555 (M+H); ElementaryAnalysis: As C₃₁H₃₃N₂O₄F₃.1.1HCl.0.4H₂O; Calcd.: C, 61.86; H, 5.84; N,4.65; F, 9.47; Cl, 6.48; Found.: C, 61.88; H, 5.94; M, 4.67; F, 9.47;Cl, 6.44.

Compound 73

mp 167-170° C.; NMR (400 MHz, DMSO-d₆); δ 0.21 (2H, m), 0.52 (2H,m),0.91 (1H, m), 1.2-1.4 (3H, m), 1.58 (1H, m), 2.1-2.2 (2H, m), 2.30(1H, m), 2.49 (1H, m), 2.6-2.8 (3H, m), 2.90 (2H, s), 3.18 (1H, d,J=18.6 Hz), 3.16 (1H, s), 3.24 (1H, m), 3.65 (0.7H, m), 4.03 (1H, s),4.20 (0.3H, m), 4.68 (0.7H, d, J=8.3 Hz), 4.79 (0.3H, d, J=7.8 Hz),6.5-6.7 (1.3H, m), 6.8-6.9 (1.4H, m), 7.34 (1H, d, J=15.6 Hz), 7.51(O.3H, d, J=15.6 Hz), 7.7-7.8 (3.7H, m), 7.94 (0.3H, d, J=8.3 Hz); IR(KBr); υ 3400, 1649, 1601, 1325, 1168, 1114 cm⁻¹. Mass (FAB); m/z 555(M+H); Elementary Analysis: As C₃₁H₃₃N₂O₄F₃.0.5(C₄H₆O₆).0.3H₂O; Calcd.:C, 62.41; H, 5.81; N, 4.41; F, 8.98; Found.: C, 62.36; H, 5.80; IT,4.41; F, 8.98.

Example 64

17-cyclopropylmethyl-14β-hydroxy-4,5α-epoxy-6α-(N-methylbenzyloxycarbamido)morphinan.phosphate74 (yield: 82%) was obtained by following the procedure of example 11but using17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-methylaminomorphinaninstead of the starting material17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan4, and using benzyl chloroformate instead of 3,4-dichlorophenylacetylchloride.

mp 122-125° C.; NMR (400 MHz, DMSO-d₆); δ 0.23 (2H, m), 0.54 (2H, m),0.93 (1H, m), 1.06 (1H, m), 1.3-1.5 (3H, m), 1.75 (1H, m), 2.2-2.3 (2H,m), 2.5-2.7 (2H, m), 2.80 (3H, s), 2.7-2.9 (2H, m), 3.18 (1H, d, J=19.5Hz), 3.35 (1H, m), 4.59 (2H, m), 5.1-5.2 (2H, m), 6.60 (1H, d, J=7.3Hz), 6.70 (1H, d, J=7.3 Hz), 7.10 (1H, t, J=7.3 Hz), 7.3-7.4 (5H, m); IR(KBr); υ 3400, 1692, 1462, 1350, 1245, 1120 cm⁻¹. Mass (FAB); m/z 474(M+H); Elementary Analysis: As C₂₉H₃₄N₂O₄.H₃PO₄.0.7H₂O; Calcd.: C,59.52; H, 6.61; N, 4.78; P, 5.29; Found.: C, 59.51; H, 6.56; N, 4.78; P,5.60.

Example 65

17-Cyclopropylmethyl-7,8-didehydro-4,5α-epox-14β-hydroxy-3-methoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan75

540 mg of17-cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-methylamino)morphinan14 and 0.31 ml of triethylamine was dissolved in 10 ml of chloroformfollowed by addition of 250 mg of trans-3-(3-furyl)acryloyl chloride andstirring for 30 minutes at room temperature. The resulting solution wasneutralized by addition of saturated aqueous sodium bicarbonate followedby extraction with chloroform. The organic layer was washed withsaturated brine, dried and concentrated. The resulting residue wasseparated and purified by column chromatography [silica gel;chloroform˜chloroform:methanol (100:1)] to obtain 610 mg of crudecrystal. This was then recrystallized from dichloromethane-ether toobtain 580 mg of the target compound (yield: 81%).

mp 199-201° C.; NMR (400 MHz, CDCl₃); δ 0.19 (2H, m) 0.60 (2H, m), 0.93(1H, m), 1.58 (1H, m), 1.74 (1H, m), 2.27-2.64 (4H, m), 2.78 (1H, m),3.00 (3H, s), 3.09 (1H, d, J=18.6 Hz), 3.40 (1H, m), 3.82 (3H, s), 4.97(1H, br s, OH), 5.14 (1H, d, J=6.8 Hz), 5.70-5.77 (2H, m), 5.83 (1H, m),6.56 (1H, d, J=8.3 Hz), 6.61 (1H, d, J=1.5 Hz), 6.66 (1H, d, J=15.3 Hz),6.67 (1H, d, J=8.3 Hz), 7.42 (1H, br s), 7.63 (1H, d, J=15.3 Hz), 7.65(1H, br s); IR (KBr); υ 3338, 1659, 1638, 1404, 1282, 1205, 1160, 1122,1054, 1017, 980, 808 cm⁻¹. Mass (EI); m/z 488 (M+).

Example 6617-Cyclopropylmethyl-7,8-didehydro-4,5α-epoxy-3,14β-dihydroxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinanehydrochloride76

300 mng of17-cyclopropylinethyl-7,8-didehydro-4,5α-epoxy-14β-hydroxy-3-inethoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan75 was dissolved in 5 ml of anhydrous dichloromethane and cooled to 0°C. 3.7 ml of a dichloromethane solution of boron tribromide (1.0 M) wasthen added followed by stirring for 2 hours (at room temperature.). Thereaction solution was cooled to 0° C. followed by addition of 6 ml of28% aqueous ammonia:water (1:4). After stirring for 30 minutes at 0° C.,the reaction solution was extracted with chloroform and methanol (3:1).The organic layer was washed with saturated brine, dried andconcentrated, and the resulting residue was purified with columnchromatography [silica gel; chloroform˜chloroform:methanol:28% aqueousammonia (100:2:0.2)] to obtain 350 mg of crude crystal. This was thenrecrystallized from dichloromethane, methanol and ethyl acetate toobtain 265 mg of a free base of the target compound. 238 mg of theresulting crystal was dissolved in 5 ml of methanol and concentratedafter adding of an excess amount of methanol solution of hydrochloride.The residue was recrystallized from methanol to obtain 159.3 mg of thetarget compound (yield: 57%).

mp 251° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.43 (1H, m), 0.53(1H, m), 0.62 (1H, m), 0.72 (1H, m), 1.07 (1H, m), 1.69-1.82 (1H, m),2.54-3.02 (4H, m), 2.91 (3H, s), 3.08-3.18 (1H, m), 3.30-3.44 (2H, m),4.07 (0.3H, m), 4.12 (0.7H, m), 4.94 (0.7H, d, J=6.8 Hz), 5.21 (0.3H, d,J=7.3 Hz), 5.49 (0.7H, m), 5.76 (0.3H, m), 5.83-5.94 (2H, m), 6.52-6.57(1H, m), 6.69-6.76 (1.6H, m), 6.95 (0.7H, d, J=15.3 Hz), 7.05 (0.7H, d,J=2.0 Hz), 7.31 (0.3H, br s, OH), 7.46 (0.7H, br s, OH), 7.51 (1H, d,J=15.3 Hz), 7.70 (0.3H, br s), 7.74 (0.7H, br s), 8.09 (1H, br s),8.90-9.06 (1H, m, NH+), 9.33 (0.3H, br s, OH), 9.34 (0.7H, br s, OH). IR(KBr); υ 3422, 3190, 1653, 1600, 1504, 1473, 1406, 1321, 1160, 118,1023, 949, 8 70, 799 cm⁻¹. Mass (FAB); m/z 475 ((M+H)+); ElementaryAnalysis: As C₂₈H₃₀N₂O₅.HCl; Calcd.: C, 65.81; H, 6.11; Cl, 6.94; N,5.48. Found.: C, 65.62; H, 6.19; Cl, 6.82; N, 5.61.

Example 67

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-5β-methyl-6α-[trans-3-(3-furyl)acrylamido]morphinan.0.5tartrate 77 (yield: 40%) was obtained by following the procedure ofexample 11 but using17-cyclopropylmethyl-3,14-dihydroxy-4,5α-epoxy-5β-methyl-6α-aminomorphinan19 instead of the starting material of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan4, and using trans-3-(3-furyl)acryloyl chloride instead of3,4-dichlorophenylacetyl chloride.

mp>170° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.31 (2H, m), 0.53(2H, m), 0.81-0.97 (2H, m), 1.33-1.52 (3H, m), 1.39 (3H, s), 1.70 (1H,m), 2.21-2.33 (2H, m), 2.41-2.83 (4H, m), 3.06 (1H, br d, J=18.6 Hz),3.25 (1H, m), 3.48 (3H, br s, 3OH), 4.03 (1H, S), 4.27 (1H, m), 6.49(1H, d, J=8.3 Hz), 6.54 (1H, d, J15.6 Hz), 6.61 (1H, d, J=8.3 Hz), 6.71(1H, d, J=1.5 Hz), 7.34 (1H, d, J=15.3 Hz), 7.46 (1H, d, J=9.3 Hz), 7.73(1H, br s), 8.01 (1H, s), 8.85 (1H, br s, NH+). IR (KBr); υ 3398, 1665,1611, 1508, 1462, 1352, 1245, 1158, 1123, 1062, 870, 803 cm⁻¹. Mass(FAB); m/z 477 ((M+H)+); Elementary Analysis: AsC₂₈H₃₂N₂O₅.0.5C₄H₆O₆.1.0H₂O; Calcd.: C, 63.26; H, 6.55; N, 4.92. Found.:C, 63.33; H, 6.43; N, 4.79.

Example 6817-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan.hydrochloride 78

21.12 g (0.0404 mol) of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylamino)morphinan.phthalate10 was dissolved in 110 ml of water. After adding 110 ml of THF and 8.75g (0.0808 mol) of sodium carbonate, the atmosphere of reaction systemwas replaced to argon. Then, 6.96 g of trans-3-(3-furyl)acryloylchloride (0.04444 mol) was dissolved in 40 ml of THF and added dropwise.After stirring for 30 minutes, 40 ml of methanol and 54 ml of 3 Naqueous sodium hydroxide were added and stirred for 1 hour. 350 ml ofethyl acetate and 250 ml of saturated aqueous sodium bicarbonate wereadded to the reaction solution to separate, and the aqueous layer wasre-extracted with 100 ml of ethyl acetate. After washing with 200 ml ofsaturated brine, the resulting organic layer was dried with sodiumsulfate and concentrated. The residue was dissolved in 630 ml of ethylacetate while heating, and after dissolving, 150 ml was distilled offwhile heating. The resulting solution was allowed to stand andrecrystallized to obtain 15.47 g of the free base of the targetcompound. 9.03 g of this free base was suspended in 90 ml of ethanol.After then adding 18.7 ml of 1 N aqueous hydrochloric acid, theresulting solution was concentrated and dried to obtain 9.72 g of thetarget compound (yield: 80%).

mp 187° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.42 (1H, m), 0.51(1H, m), 0.60 (1H, m), 0.68 (1H, m), 1.07 (1H, m), 1.26 (0.4H, m),1.32-1.50 (3.6H, m), 1.73 (1H, br d, J=13.7 Hz), 2.13 (1H, m), 2.40-2.60(3H, m), 2.88 (1H, m), 2.92 (1.8H, s), 3.06 (1H, br d, J=13.18 Hz), 3.16(1.2H, s), 3.59 (0.6H, m), 3.86 (1H, m), 4.19 (0.4H, m), 4.86 (0.6H, d,J=7.8 Hz), 4.92 (0.4H, d, J=7.8 Hz), 6.35 (0.6H, d, J=15.6 Hz), 6.40(0.4H, br s), 6.50 (0.6H, br s), 6.62 (0.6H, s), 6.64 (0.4H, d, J=8.3Hz), 6.71 (1H, d, J=8.3 Hz), 6.85 (0.6H, d, J=8.3 Hz), 6.90 (0.4H, d,J=15.1 Hz), 6.99 (0.4H, s), 7.22 (0.6H, d, J=15.6 Hz), 7.36 (0.4H, d,J=15.1 Hz), 7.66 (0.6H, s), 7.72 (0.4H, s), 7.92 (0.6H, s), 8.03 (0.4H,s), 8.85 (1H, br s), 9.28 (0.4H, s), 9.68 (0.6H, s); IR (KBr); υ 3376,1653, 1506, 1599, 1410, 1323, 1158, 1127, 1033, 872, 799 cm⁻¹. Mass(FAB); m/z 477 (M+H); Elementary Analysis: As C₂₈H₃₂N₂O₅.HCl0.2H₂O;Calcd.: C, 65.10; H, 6.52; N, 5.42; Cl, 6.86. Found.: C, 6 5.11; H,6.63; N, 5.60; Cl, 6.80.

Examples 69-71

17-Cyclopropylmethyl-3,14β-dihydroxy-4,9α-epoxy-6β-[trans-3-(3-furyl)acrylamido]morphinan.hydrochloride79,17-cyclopropylmethyl-3-hydroxy-4,5α-epoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan.hydrochloride80, and17-cyclopropylmethyl-3-hydroxy-4,5α-epoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamnido]morphinan.hydrochloride81 were obtained by following the procedure of example 68 but using17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-aminomorphinan (J. B.Jiang, R. N. Hanson, P. S. Portoghese and A. E. Takedori, J. Med. Chem., 20, 1100 (1977)),17-cyclopropylmethyl-3-hydroxy-4,5α-epoxy-6β-methylaminomorphinan 20,and 17-cyclopropylmethylod-3-hydroxy-4,5α-epoxy-6α-methylaminomorphinan21 instead of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-(N-methylamino)morphinan10.phthalate.

Compound 79

mp 240° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.41 (1H, m), 0.52(1H, m), 0.59 (1H, m), 0.67 (1H, m), 1.07 (1H, m), 1.32-1.49 (2H, rn),1.57 (1H, m), 1.68-1.83 (2H, m), 2.37-2.47 (2H, m), 2.86 (1H, m),2.98-3.12 (2H, m), 3.27-3.39 (2H, m), 3.52 (1H, m), 3.86 (1H, br d,J=4.9 Hz), 4.60 ((H, d, J=7.8 Hz), 6.23 (1H, br s ), 6.33 (1H, d, J=15.6Hz), 6.65 (1H, d, J=7.8 Hz), 6.72 (1H, d, J=7.8 Hz), 6.73 (1H, br s),7.32 (1H, d, J=15.6 Hz), 7.74 (1H, br s), 8.01 (1H, s), 8.40 (1H, d,J=7.8 Hz), 8.86 (1H, m, NH+), 9.36 (1H, s, OH). IR (KBr); υ 3376, 3244,1663, 1620, 1560, 1508, 1460, 1377, 1340, 1241, 1156, 1127, 1035, 980,872, 795 cm⁻¹. Mass (FAB); m/z 463 ((M+H)+). Elementary Analysis: AsC₂₇H₃₀N₂O₅.HCl.0.2H₂O; Calcd.: C, 64.52; H, 6.30; Cl, 7.05; N, 5.57;Found.: C, 64.50; H, 6.39; Cl, 7.00; N, 5.53.

Compound 80

mp 225-230° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.38 (1H, m),0.51 (1H, m), 0.63 (2H, m), 0.97 (1H, m), 1.21 (1H, m), 1.40-1.72 (3.8H,m), 2.29 (1H, m), 2.40-2.52 (1.2H, m), 2.57 (0.2H, m), 2.70 (0.8H, m),2.80-2.96 (1.2H, m), 2.89 (2.4H, s), 3.00-3.18 (1.6H, m), 3.14 (0.6H,s), 3.18-3.35 (2.2H, m), 3.48 (0.8H, m), 3.95-4.10 (1.2H, m), 4.65-4.95(1H, m), 6.27-8.32 (7H, m); IR (KBr); υ 3370, 1651, 1593, 1321, 1156,872 cm⁻¹. Mass (FAB); m/z 461 (M+H); Elementary Analysis: AsC₂₈H₃₂N₂O₄.1.7HCl.0.5H₂O; Calcd.: C, 63.27; H. 6.58; N, 5.27; Cl, 11.34;Found.: C, 63.24; H, 6.60; N, 5.09; Cl, 11.55.

Compound 81

mp 210-215° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.38 (1H, m),0.48 (1H, m), 0.65 (2H, m), 0.98 (1H, m), 1.16 (2H, m), 1.32 (1H, m),1.62-1.90 (2H, m), 2.23 (1H, m), 2.68 (0.7H, m), 2.8-3.4 (7.2H, m), 3.04(2.1H, s), 4.01-4.10 (1H, m), 4.52 -4.81 (2H, m), 6.6-8.3 (7H, m); IR(KBr); υ 3380, 1651, 1591, 1323, 1160, 872 cm⁻¹. Mass (FAB); m/z 461(M+H); Elementary Analysis: As C₂₈H₃₂N₂O₄.1.4HCl.0.5H₂O; Calcd.: C,64.60; H. 6.66; N, 5.38; Cl, 9.53; Found.: C, 64.78; H, 6.82; N, 5.01;Cl, 9.29.

Example 72

17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-trans-3-(2-thienyl)acrylamido]morphinan.tartrate82 (yield: 84%) was obtained by following the procedure of example 68but using trans-3-(2-thienyl)acryloyl chloride instead oftrans-3-(3-furyl)acryloyl chloride.

mp 178-181° C.; NMR (400 MHz, DMSO-d₆); δ 0.22 (2H, brs), 0.53 (2H, m),0.91 (1H, mn), 1.2-1.4 (3H, m), 1.58 (1H, d, J=10.4 Hz), 2.14 (2H, m),2.27 (1H, m), 2.50 (1H, m), 2.6-2.8 (3H, m), 2.88 (1.8H, s), 3.08 (1H,d, J=17.1 Hz), 3.11 (1.2H, s), 3.24 (1H, mn), 3.59 (0.6H, m), 4.02 (1H,s), 4.20 (0.4H, mn), 4.66 (0.6H, d, J=8.6 Hz), 4.76 (0.4H, d, J=8.6 Hz),6.42 (0.6H, d, J15.3 Hz), 6.48 (0.4H, d, J=12.2 Hz), 6.57 (1H, d, J=7.9Hz), 6.75 (0.6H, d, J=7.9 Hz), 6.85 (0.4H, d, J=15.3 Hz), 7.07 (0.6H, t,J=3.7 Hz), 7.12 (0.4H, t, J=4.9 Hz), 7.32 (0.6H, d, J=3.1 Hz), 7.45-7.48(1H, mn), 7.58-7.67 (1.4H, m); IR (KBr); υ 3350, 1636, 1590, 1460, 1035cm⁻¹; Mass (FAB); m/z 493 (M+H); Elementary Analysis: ASC₂₈H₃₂N₂O₄S.0.5(C₄H₆O₆).0.5H₂O; Calcd. : C, 62.48; H, 6.29; N, 4.86; S,5.56; Found.: C, 62.32; H, 6.36; N, 4.92; S, 5.57.

Example 7317-Cyclopropylmnethyl-3,14-β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-nitrophenylacetarnido)morphinan.hydrochloride83

567.1 mg (1.59 mmol) of17-cyclopropylmnethyl-3,14β-dihydroxy-4,5α-epoxy-6α-methylaminomorphinan4 and 577.9 mg (3.19 mmol) of 3-nitrophenylacetic acid were dissolved in18 ml of chloroform followed by the addition of 657.0 mg (3.18 mmol) ofdicyclohexylcarbodiimide and 10.0 mg (0.082 mmol) of4-(N,N-dimethylamino)pyridine to this solution and stirring for 1 hourat room temperature. The solid that formed in the reaction solution wasfiltered out, the residue was washed with chloroform, and the filtrateand washing were combined and concentrated. The resulting solid wasdissolved in a mixed solution of methanol and chloroform (4:1) followedby the addition of 445 mg (3.22 mmol) of potassium carbonate andstirring for 2 hours at room temperature. 15 ml of water was added tothe reaction solution followed by extraction with chloroform (3×15 ml).The organic layers were then combined and concentrated to obtain 2.27 gof solid. This solid was then purified with column chromatography[silica gel 80 g; chloroform-methanol (40:1→20:1)] to obtain 717.4 mg ofthe free base of the target compound (yield: 87%). This crystal was thendissolved in methanol followed by addition of methanol solutionsaturated with hydrogen chloride gas. The precipitated crystal was thenfiltered to obtain 300.5 mg of the target compound (yield: 34%). Inaddition, the crystal resulting from concentration of this filtrate wasthen recrystallized from methanol to further obtain 354.0 mg of thetarget compound (yield: 40%). Both of these compounds were then combinedto obtain 654.5 mg of the target compound (yield: 74%).

mp>210° C. (decomposition, methanol); NMR (400 MHz, DMSO-d₆); δ 0.39(1H, m), 0.47 (1H, m), 0.61 (1H, m), 0.68 (1H, m), 1.06 (1H, m), 1.17(1H, m), 1.37 (1H, m), 1.50-1.64 (2H, m), 1.94 (1H, m), 2.43 (1H, m),2.68 (1H, m), 2.82 (0.6H, s), 2.90-3.14 (3H, m), 3.00 (2.4H, s),3.22-3.38 (2H, m), 3.90-4.10 (3H, m), 4.54 (0.2H, m), 4.63 (0.8H, d,J=3.3 Hz), 4.82 (0.2H, m), 4.98 (0.8H, m), 6.28 (1H, br s, OH), 6.58(1H, d, J=7.8 Hz), 6.75 (1H, d, J=7.8 Hz), 7.62 (0.8H, dd, J=7.8, 7.8Hz), 7.65 (0.2H, dd, J=7.8, 7.8 Hz), 7.71 (0.8H, d, J=7.8 Hz), 7.75(0.2H, d, J=7.8 Hz), 8.13 (1H, d, J=7.8 Hz), 8.14 (1H, br s), 8.84 (1H,m, NH+), 9.36 (1H, S, OH). IR (KBr); υ 3388, 1618, 1528, 1466, 1352,1321, 1120, 1036, 920, 806 cm⁻¹. Mass (FAB); m/z 520 ((M+H)+).Elementary Analysis: As C₂₉H₃₃N₃O₆.HCl; Calcd.: C, 62.64; H, 6.16; N,7.56; Cl, 6.38. Found.: C, 62.25; H, 6.39; N, 7.68; Cl, 6.20.

Examples 74-88

17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-phenylpropiolamido)morphinan.hydrochloride84 (yield: 16%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methylcyclohexylacetamido)morphinan.hydrochloride85 (yield: 55%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3,4-dichlorocinnamamido)morphinan.hydrochloride 86 (yield: 78%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-4-nitrophenylacetamido)morphinan.hydrochloride87 (yield: 83%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-2-bromophenylacetamido)morphinan.hydrochloride88 (yield: 81%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan.tartrate89 (yield: 39%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-4-pyridylacetamido)morphinan.2hydrochloride 90 (yield: 83%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[N-methyl-trans-3-(3-thienyl)acrylamido]morphinan.tartrate91 (yield: 40%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-2-pyridylacetamido)morphinan.2hydrochloride 92 (yield: 82%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-pyridylacetamido)morphinan.hydrochloride 93 (yield: 92%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-cyclohexylpropionamido)morphinan.hydrochloride94 (yield: 45%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-trans-2-hexenamido)morphinan.tartrate95 (yield: 46%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-fluorocinnamamido)morphinan.tartrate96 (yield: 79%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-nitrocinnamamido)morphinan.phosphate97 (yield: 40%) and17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methylbenzoylacetamido)morphinan.tartrate98 (yield: 37%) were obtained by following the procedure of example 73but using phenylpropiolic acid, cyclohexylacetic acid,trans-3,4-dichlorocinnamic acid, 4-nitrophenylacetic acid,2-bromophenylacetic acid, trans-3-(3-furyl)acrylic acid, 4-pyridylaceticacid, trans-3-(3-thienyl)acrylic acid, 2-pyridylacetic acid,3-pyridylacetic acid, 3-cyclohexylpropionic acid, trans-2-hexenoic acid,3-fluorocinnamic acid, 3-nitrocinnamic acid and benzoylacetic acidinstead of 3-nitrophenylacetic acid.

Compound 84

mp 206.0-209.0° C. (decomposition, ether); NMR (400 MHz, DMSO-d₆); δ0.41 (1H, m), 0.49 (1H, m), 0.62 (1H, m), 0.69 (1H, m), 1.08 (1H, m),1.19 (0.5H, m), 1.27 (0.5H, m), 1.45˜1.72 (3H, m), 1.95 (0.5H, m), 2.02(0.5H, m), 2.48 (1H, m), 2.71 (1H, m), 2.92 (1.5H, s), 2.94˜3.06 (2H,m), 3.12 (1H, dd, J=19.5, 6.7 Hz), 3.24 (1.5H, S), 3.27˜3.38 (2H, m),3.95 (1H, dd, J=15.6, 6.7 Hz), 4.71 (0.5H, d, J=3.7 Hz), 4.81 (0.5H, d,J=3.7 Hz), 4.92 (0.5H, br d, J=13.4 Hz), 5.09 (0.5H, br d, J=13.4 Hz),6.32 (0.5H, s), 6.42 (0.5H, s), 6.61 (0.5H, d, J=7.9 Hz), 6.62 (0.5H, d,J=7.9 Hz), 6.74 (0.5H, d, J=7.9 Hz), 6.75 (0.5H, d, J=7.9 Hz), 7.49 (1H,t, J=7.3 Hz), 7.52˜7.57 (2H, m), 7.66 (1H, d, J=8.5 Hz), 7.72 (1H, d,J=7.3 Hz), 8.85 (0.5H, br s), 8.93 (0.5H, br s), 9.37 (1H, s). IR (KBr);υ 3400, 2952, 2216, 1613, 1493, 1377, 1321, 1120, 1036, 692 cm⁻¹. Mass(FAB); m/z 485 (M+H)+. Elementary Analysis: As C₃₀H₃₂N₂O₄.1.5HCl.0.8H₂O;Calcd.: C, 66.61; H, 6.48; N, 5.18; Cl, 7.54. Found.: C, 66.42; H, 6.55;N, 5.19; Cl, 7.72.

Compound 85

mp 245.0-248.0° C. (decomposition, ether); NMR (400 MHz, DMSO-d₆); δ0.40 (1H, m), 0.47 (1H, m), 0.61 (1H, m), 0.68 (1H, m), 0.93˜1.35 (8H,m), 1.53˜1.74 (8H, m), 1.90 (1H, m), 2.22 (2H, dd, J=6.8, 2.4 Hz),2.39˜2.54 (2H, m), 2. 69 (1H, m), 2.79 (0.6H, s), 2.88 (2.4H, s), 2.92(1H, m), 3.03 (1H, br d, J=13.2 Hz), 3.09 (1H, dd, J=20.4, 7.6 Hz), 3.39(1H, m), 3.87 (1H, d, J=6.4 Hz), 4.48 (0.2H, m), 4.60 (0.8H, d, J=3.9Hz), 4.73 (0.2H, br s), 4.98 (0.8H, dt, J=14.2, 3.9 Hz), 6.16 (0.8H, s),6.38 (0.2H, s), 6.58 (0.8H, d, J=8.3 Hz), 6.59 (0.2H, d, J=7.8 Hz), 6.71(0.8H, d, J=7.8 Hz), 6.72 (0.2H, d, J=8.3 Hz), 8.79 (1H, br s), 9.28(0.8H, s), 9.31 (0.2H, s). IR (KBr); 3400, 2928, 2856, 1615, 1508, 1317,1120, 804 cm⁻¹. Mass (FAB); m/z 481 (M+H)+. Elementary Analysis: AsC₂₉H₄₁N₂O₄Cl.0.4H₂O; Calcd.: C, 66.43; H, 8.04; N, 5.34; Cl, 6.76.Found.: C, 66.33; H, 7.81; N, 5.35; Cl, 6.97.

Compound 86

mp 249-258° C. (decomposition, methanol); NMR (400 MHz, DMSO-d₆); δ0.31-0.43 (1H, m), 0.43-0.54 (1H, m), 0.54-0.66 (1H, m), 0.66-0.76 (1H,m), 0.99-1.12 (1H, m), 1.12-1.33 (1H, m), 1.33-1.50 (1H, m), 1.50-1.70(2H, m), 1.86-2.03 (1H, m), 2.40-2.50 (1H, m), 2.61-2.78 (1H, m),2.87-2.99 (1H, m), 2.90 (0.6H, s), 2.99-3.19 (2H, m), 3.09 (2.4H, s),3.19-3.39 (2H, m), 3.92 (1H, br d, J=5.9 Hz), 4.63 (0.2H, m), 4.73(0.8H, d, J=3.9 Hz), 4.92 (0.2H, brs), 5.04 (0.8H, dt, J=14.2, 4.0 Hz),6.27 (0.8H, br s), 6.46 (0.2H, br s), 6.60 (1H, d, J=7.8 Hz), 6.73 (1H,d, J=7.8 Hz), 7.32 (0.2H, d, J=15.1 Hz), 7.38 (0.8H, d, J=15.1 Hz), 7.47(0.2H, d, J=15.1 Hz), 7.49 (0.8H, d, J=15.1 Hz), 7.64-7.73 (1H, m), 7.75(1H, dd, J=8.3, 2.0 Hz), 8.04 (0.2H, s), 8.13 (0.8H, d, J=2.0 Hz), 8.82(1H, br s), 9.31 (0.8H, s), 9.34 (0.2H, s), IR (KBr); υ 1649, 1599,1510, 1475, 1377, 1317, 1120, 1033 cm⁻¹. Mass (FAB); m/z 555 ((M+H)+).Elementary Analysis: As C₃₀H₃₃N₂O₄Cl₃; Calcd.: C, 60.87; H, 5.62; N,4.73; Cl, 17.97; Found.: C, 60.87; H, 5.82; N, 4.73; Cl, 17.75.

Compound 87

mp>190° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.39 (1H, m), 0.47(1H, m), 0.61 (1H, m),0.68 (1H, m), 1.05 (1H, m), 1.18 (1H, m), 1.37(1H, m), 1.46-1.63 (2H, m), 1.93 (1H, m), 2.43 (1H, m), 2.67 (1H, m),2.82 (0.6H, s), 2.90-3.14 (3H, m), 2.98 (2.4H, s), 3.21-3.39 (2H, m),3.88-4.07 (3H, m), 4.50 (0.2H, m), 4.60-4.67 (1H, m), 4.98 (0.8H, m),6.27 (0.8H, br s, OH), 6.58 (1H, d, J=7.8 Hz), 6.59 (0.2H, br s, OH),6.74 (1H, d, J=7.8 Hz), 7.53 (1.6H, d, J=8.8 Hz), 7.58 (0.4H, d, J=8.8Hz), 8.20 (1.6H, d, J=8.8 Hz), 8.23 (0.4H, d, J=8.8 Hz), 8.83 (1H, m,NH+), 9.34 (1H, br s, OH). IR (KBr); υ 3358, 1611, 1520, 1468, 1346,1323, 1118, 1035, 919, 820 cm⁻¹. Mass (FAB); m/z 520 ((M+H)+);Elementary Analysis: As C₂₉H₃₃N₃O₆.HCl.0.7H₂O; Calcd.: C, 61.25; H,6.27; N, 7.39; Cl, 6.23. Found.: C, 61.24; H, 6.38; N, 7.18; Cl, 6.37.

Compound 88

mp 230° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.40 (1H, m), 0.46(1H, m), 0.60 (1H, m), 0.68 (1H, m), 1.05 (1H, m), 1.18 (1H, m), 1.38(1H, m), 1.50-1.64 (2H, m), 1.93 (1H, m), 2.42 (1H, m), 2.69 (1H, m),2.84 (0.6H, s), 2.94 (1H, m), 3.01 (2.4H, s), 3.02-3.14 (2H, m),3.21-3.33 (2H, m), 3.82-3.97 (3H, m), 4.57 (0.2H, m), 4.61 (0.8H, d,J=3.7 Hz), 4.84 (0.2H, m), 4.98 (0.8H, m), 6.24 (0.8H, br s), 6.46(0.2H, br s), 6.58 (1H, d, J=7.9 Hz), 6.75 (1H, d, J=7.9 Hz), 7.21 (1H,m), 7.30-7.38 (2H, m), 7.60 (1H, m), 8.82 (1H, br s), 9.34 (0.8H, S),9.35 (0.2H, s). IR (KBr); υ 3120, 1620, 1508, 1473, 1377, 1317, 1118,1027, 752 cm⁻¹. Mass (FAB); m/z 553 ((M+H)+) Elementary Analysis: AsC₂₉H₃₃N₂O₄Br.HCl.0.4H₂O; Calcd.: C, 58.33; H, 5.87; N, 4.69; Cl, 5.94;Br, 13.38. Found.: C, 58.52; H, 5.76; N, 4.77; Cl, 6.07; Br, 13.03.

Compound 89

mp 243.0-254.0° C. (decomposition, diethylether); NMR (400 MHz,DMSO-d₆); δ 0.10-0.30 (2H, m), 0.44-0.63 (2H, m), 0.83-0.99 (1H, m),0.90-1.30 (1H, m), 1.30-1.42 (1H, m), 1.42-1.60 (2H, m), 1.69-1.83 (1H,m), 2.12-2.41 (2H, m), 2.41-2.65 (2H, m), 2.65-2.82 (2H, m), 2.82-2.98(1H, m), 3.05 (3H, s), 3.05-3.16 (1H, m), 3.16-3.39 (1H, m), 2.80-3.80(1H, br s), 4.07 (1H, s), 4.55 (0.2H, m), 4.63 (0.8H, d, J=2.9 Hz), 4.68(0.2H, br s), 4.96 (0.8H, dt, J=13.6, 4.0 Hz), 6.52 (1H, d, J=8.3 Hz),6.63 (1H, d, J=7.8 Hz), 6.72-6.87 (0.4H, m), 6.96 (0.8H, d, J=15.1 Hz),7.01 (0.8H, s), 7.43 (1H, d, J=15.1 Hz), 7.72 (0.8H, s), 7.70-7.78 (1H,m), 8.80-9.60 (1H, br s); IR (KBr); υ 1651, 1597, 1510, 1460, 1377,1160, 1120, 1038, 801 cm⁻¹. Mass (FAB); m/z 477 ((M+H)+). ElementaryAnalysis: As C₃₀H₃₅N₂O₈.0.8H₂O; Calcd.: C, 63.66; H, 6.52; N, 4.95;Found.: C, 63.42; H, 6.50; N, 4.87.

Compound 90

mp 200° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.40 (1H, m), 0.47(1H, m), 0.61 (1H, m), 0.68 (1H, m), 1.06 (1H, m), 1.18 (1H, m), 1.38(1H, m), 1.50-1.64 (2H, m), 1.95 (1H, m), 2.42 (1H, m), 2.67 (1H, m),2.83 (0.6H, s), 3.00 (2.4H, s), 2.90-3.13 (3H, m), 3.23-3.36 (2H, m),3.50-4.30 (4H, m), 4.51 (0.2H, m), 4.62 (0.8H, d, J=3.9 Hz), 4.89 (0.2H,m), 4.97 (0.8H, m), 6.32 (1H, br s), 6.59 (1H, d, J=8.3 Hz), 6.75 (1H,d, J=8.3 Hz), 7.81 (2H, d, J=6.8 Hz), 8.79 (2H, d, J=6.8 Hz), 8.85 (1H,br s), 9.38 (1H, br s). IR (KBr); υ 3390, 1620, 1510, 1460, 1321, 1120,803 cm⁻¹. Mass (EI); m/z 475 (M+); Elementary Analysis: AsC₂₈H₃₃N₃O₄.1.8HCl.0.4H₂O; Calcd.: C, 61.32; H, 6.54; N, 7.66; Cl, 11.64.Found.: C, 61.23; H, 6.68; N, 7.55; Cl, 11.59.

Compound 91

mp 249.0-250.0° C. (decomposition, methanol); NMR (400 MHz, DMSO-d₆); δ0.10-0.30 (2H, m), 0.44-0.63 (2H, m), 0.83-0.99 (1H, m), 1.10-1.32 (2H,m), 1.32-1.42 (1H, m), 1.42-1.67 (3H, m), 1.69-1.86 (1H, m), 2.18-2.41(2H, m), 2.41-2.66 (2H, m), 2.66-2.84 (2H, m), 2.84-2.96 (1H, m), 3.06(3H, s), 3.05-3.16 (1H, m), 3.30 (1H, br s), 4.06 (1H, s), 4.59 (0.2H,m), 4.64 (0.8H, d, J=2.9 Hz), 4.65 (0.2H, brs), 4.97 (0.8H, dt, J=13.7,2.5 Hz), 6.52 (1H, d, J=7.8 Hz), 6.63 (1H, d, J=8.3 Hz), 6.91 (0.2H, m),7.07 (0.8H, d, J=15.1 Hz), 7.41-7.50 (0.2H, m), 7.53 (1H, d, J=15.1 Hz),7.61 (1.8H, s), 7.89 (1H, s), 8.52-9.48 (1H, br s); IR (KBr); υ 1638,1597, 1508, 1460, 1402, 1321, 1118, 1069, 1038, 789 cm⁻¹. Mass (FAB);m/z 493 ((M+H)+); Elementary Analysis: As C₃₀H₃₅N₂O₇S.1.2H₂O; Calcd.: C,61.14; H, 6.40; N, 4.75; S, 5.44; Found.: C, 61.20; H, 6.39; N, 4.69; S,5.29.

Compound 92

mp 190° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.40 (1H, m), 0.47(1H, m), 0.61 (1H, m), 0.68 (1H, m), 1.06 (1H, m), 1.20 (1H, m), 1.38(1H, m), 1.48-1.64 (2H, m), 1.95 (1H, m),2.41 (1H, m), 2.67 (1H, m),2.83 (0.6H, s), 3.02 (2.4H, s), 2.90-3.15 (3H, m), 3.22-3.36 (2H, m),3.40-3.85 (1H, br), 3.93-4.40 (3H, m), 4.58 (0.2H, m), 4.60 (0.8H, d,J=3.9 Hz), 4.97 (1H, m), 6.32 (1H, br s), 6.59 (1H, d, J=8.3 Hz), 6.76(1H, d, J=8.3 Hz), 7.74-7.83 (2H, m), 8.36 (1H, m), 8.79 (1H, br d,J=3.9 Hz), 8.94 (1H, brs), 9.40 (1H, br s). IR (KBr); υ 3380, 1638,1508, 1460, 1321, 1120, 768 cm⁻¹; Mass (FAB); m/z 476 ((M+H)+).Elementary Analysis: As C₂₈H₃₃N₃O₄.1.8HCl.0.6H₂O; Calcd.: C, 60.92; H,6.57; N, 7.61; Cl, 11.56. Found.: C, 60.91; H, 6.82; N, 7.47; Cl, 11.52.

Compound 93

mp 195° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.40 (1H, m), 0.47(1H, m), 0.61 (1H, m), 0.68 (1H, m), 1.08 (1H, m), 1.19 (1H, m), 1.38(1H, m), 1.48-1.64 (2H, m), 1.95 (1H, m), 2.42 (1H, m), 2.65 (1H, m),2.83 (0.6H, s), 3.02 (2.4H, s), 2.88-3.15 (3H, m), 3.22-3.36 (2H, m),3.45-3.80 (1H, br), 3.95-4.23 (3H, m), 4.60 (1H, m), 4.97 (1H, m), 6.32(1H, br s), 6.59 (1H, m), 6.77 (1H, m), 7.91 (1H, m), 8.32 (1H, m),8.74-8.82 (2H, m), 8.94 (1H, br s), 9.38 (1H, br s). IR (KBr); υ 3410,1626, 1475, 1321, 1120, 1036, 919, 806, 683 cm⁻¹. Mass (FAB); m/z 476((M+H)+). Elementary Analysis: As C₂₈H₃₃N₃O₄.1.8HCl.0.75H₂O; Calcd.: C,60.63; H, 6.60; N, 7.57; Cl, 11.50. Found.: C, 61.01; H, 6.82; N, 7.17;Cl, 11.49.

Compound 94

mp>265° C. (decomposition); NMR (400 MHz, CD₃OD); δ 0.49 (2H, m), 0.73(1H, m), 0.83 (1H, m), 0.90-1.03 (2H, m), 1.09 (1H, m), 1.15-1.41 (5H,m), 1.43-1.58 (3H, m), 1.63-1.83 (7H, m), 1.92 (1H, m), 2.38-2.52 (2H,m), 2.64 (1H, m), 2.84-3.05 (2H, m), 2.93 (0.6H, S), 3.02 (2.4H, s),3.05-3.21 (2H, m), 3.23-3.40 (2H, m), 3.98 (1H, m), 4.57 (0.2H, m), 4.75(1H, br d, J=3.4 Hz), 5.08 (0.8H, ddd, J=13.7, 3.9, 3.9 Hz), 6.67 (0.8H,d, J=8.3 Hz), 6.69 (0.2H, d, J=8.3 Hz), 6.75 (0.8H, d, J=8.3 Hz), 6.76(0.2H, d, J=8.3 Hz). IR (KBr); υ 3342, 3140, 1622, 1508, 1470, 1317,1172, 1118, 1038, 920, 907, 806 cm⁻¹. Mass (FAB); m/z 495 ((M+H)+);Elementary Analysis: As C₃₀H₄₂N₂O₄.HCl.0.18H₂O; Calcd.: C, 67.43; H,8.18; N, 5.24; Cl, 6.63. Found.: C, 67.80; H, 8.01; N, 4.84; Cl, 6.69.

Compound 95

mp 230-240° C. (decomposition); NMR (400 MHz, DMSQ-d₆); δ 0.19 (2H, m),0.45-0.58 (2H, m), 0.90 (1H, m), 0.91 (3H, t, J=7.3 Hz), 1.07-1.37 (2H,m), 1.38-1.55 (4H, m), 1.73 (1H, m), 2.13-2.27 (4H, m), 2.42-2.58 (2H,m), 2.62-2.78 (2H, m), 2.84 (0.6H, s), 2.95 (2.4H, S), 3.03 (1H, br d,J=19.0 Hz), 3.23 (1H, m), 3.50 (3H, br s, 3×OH), 4.02 (1H, s), 4.45(0.2H, m), 4.56 (0.2H, m), 4.58 (0.8H, d, J=3.4 Hz), 4.90 (0.8H, m),6.34 (0.2H, d, J=15.1 Hz), 6.45 (0.8H, d, J=15.1 Hz), 6.50 (1H, d, J=8.0Hz), 6.61 (1H, d, J=8.0 Hz), 6.65-6.73 (1H, m), 9.06 (1H, br s, NH+). IR(KBr); υ 3386, 1657, 1591, 1462, 1408, 1359, 1315, 1170, 1122, 1069,1038, 980, 920, 810 cm⁻¹. Mass (FAB); m/z 453 ((M+H)+). ElementaryAnalysis: As C₂₇H₃₆N₂O₄.0.5C₄H₆O₆.0.2H₂O; Calcd.: C, 65.57; H, 7.48; N,5.27. Found.: C, 65.54; H, 7.35; N, 5.37.

Compound 96

mp 225° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.10-0.23 (2H, m),0.43-0.60 (2H, m,), 0.82-0.98 (1H, m), 1.12-1.60 (4H, m), 1.68-1.82 (1H,m), 2.18-2.40 (2H, m), 2.62-2.80 (2H, m), 2.83-4.00 (10H, m), 4.04 (1H,s), 4.52-4.60 (0.3H, m), 4.65 (0.7H, d, J=3.4 Hz), 4.75 (0.3H, br s),4.92-5.02 (0.7H, m), 6.51 (1H, d, J=7.8 Hz), 6.62 (1H, d, J=7.8 Hz),7.10-7.26 (1H, m), 7.31 (1H, d, J=15.6 Hz), 7.40-7.57 (3H, m), 7.67 (1H,d, J=10.3 Hz), 9.07 (1H, br s). IR (KBr); υ 3400, 1644, 1586, 1462,1408, 1359, 1315, 1120, 789 cm⁻¹. Mass (FAB); m/z 505 ((M+H)+);Elementary Analysis: As C₃₀H₃₃N₂O₄F.0.5C₄H₆O₆; Calcd.: C, 66.31; H,6.26; N, 4.83; F, 3.28. Found.: C, 66.43; H, 6.37; N, 4.87; F, 3.27.

Compound 97

mp 185-200° C.; NMR (400 MHz, DMSO-d₆); δ 0.10-0.30 (2H, m), 0.45-0.62(2H, m), 0.82-1.00 (1H, m), 1.10-1.60 (4H, m), 1.70-1.85 (1H, m),2.20-2.35 (2H, m), 2.55-2.90 (5H, m), 2.92 (0.6H, s), 2.97-3.10 (1H, m),3.12 (2.4H, s), 3.23-3.37 (1H, m), 3.50-5.75 (4H, br), 4.55 (0.2H, m),4.66 (0.8H, d, J=3.4 Hz), 4.78 (0.2H, m), 4.98 (0.8H, m), 6.53 (1H, d,J=8.1 Hz), 6.64 (1H, d, J=8.l Hz). 7.29 (0.2H, d, J=15.1 Hz), 7.48(0.8H, d, J=15.4 Hz), 7.58 (0.2H, d, J=15.1 Hz), 7.63 (0.8H, d, J=15.4Hz), 7.71 (1H, t, J=8.1 Hz), 8.10-8.27 (2H, m), 8.50 (0.2H, s), 8.61(0.8H, s). IR (KBr); υ 3398, 3360, 3216, 3094, 1649, 1591, 1531, 1350,1120, 1036, 973, 812, 741; Mass (FAB); m/z 532 ((M+H)+). ElementaryAnalysis: As C₃₀H₃₃N₃O₆.H₃PO₄.1.6H₂O; Calcd.: C, 54.73; H, 6.00; N 6.38;P, 4.70. Found.: C, 54.66; H, 5.85; N, 6.28; P, 4.45.

Compound 98

mp>176° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.14-0.24 (2H, m),0.43-0.57 (2H, m), 0.81-0.95 (1H, m), 1.10-1.58 (4H, m), 1.74 (1H, m),2.16-2.31 (2H, m), 2.40-2.56 (2H, m), 2.62-2.78 (2H, m), 2.84 (0.27H,s), 2.94 (1.71H, s), 2.99-3.08 (1H, m), 3.04 (1.02H, S), 3.25 (1H, m),3.50 (3H, br s, 3×OH), 4.03 (1H, s), 4.15-4.25 (0.15H, m), 4.20 (0.51H,d, J=16.6 Hz), 4.29 (0.51H, d, J=16.6 Hz), 4.29 (0.09H, d, J=16.6 Hz),4.36 (0.09H, d, J=16.6 Hz), 4.52 (0.51H, d, J=3.9 Hz), 4.63 (0.34H, d,J=3.9 Hz), 4.72 (0.06H, m), 4.77 (0.09H, m), 4.91 (0.51H, ddd, J=13.7,3.9, 3.9 Hz), 4.98 (0.34H, ddd, J=13.7, 3.9, 3.9 Hz), 5.97 (0.06H, s),6.18 (0.34H, s), 6.50-6.56 (1H, m), 6.61-6.67 (1H, m), 7.45-8.02 (5H,m), 9.10 (1H, br s, NH+), 15.84 (0.34H, s), 15.92 (0.06H, s). IR (KBr);υ 3400, 1688, 1611, 1464, 1359, 1323, 1214, 1172, 1120, 1069, 1038, 919,806 cm⁻¹. Mass (FAB); m/z 503 ((M+H)+). Elementary Analysis: AsC₃₀H₃₄N₂O₅.0.5C₄H₆O₆.0.7H₂O; Calcd.: C, 65.12; H, 6.56; N, 4.75. Found.:C, 65.15; H, 6.43; N, 4.74.

Examples 89-94

17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methylcinnamamido)morphinan.hydrochloride99 (yield: 46%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-trans-2-hexenamido)morphinan.tartrate100 (yield: 52%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-phenylpropiolamido)morphinan.hydrochloride101 (yield: 49%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-fluorocinnamamido)morphinan.tartrate102 (yield: 81%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methylbenzoylacetamido)morphinan.tartrate103 (yield: 52%) and17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-nitrocinnamamido)morphinan.tartrate104 (yield: 47%) were obtained by following the procedure of example 73but using17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-methylaminomorphinan10 instead of the starting material of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan4, and using cinnamic acid, trans-2-hexenoic acid, phenylpropiolic acid,3-fluorocinnamic acid, benzoylacetic acid and 3-nitrocinnamic acidinstead of 3-nitrophenylacetic acid. Compound 99

mp 225° C. (decomposition); NMR (400 MHz, DMSQ-d₆); δ 0.42 (1H, m), 0.50(1H, m), 0.59 (1H, m), 0.68 (1H, m), 1.07 (1H, m), 1.20-1.50 (3.5H, m),1.72 (1H, m), 2.13 (1H, m), 2.40-2.60 (2.5H, m), 2.87 (1H, m), 2.92 (2H,s), 3.06 (2H, m),3.19 (1H, s), 3.32 (2H, m), 3.6-4.3 (2H, m), 4.85(0.7H, m), 4.92 (0.3H, m), 6.30 (1H, m), 6.68 (2H, m), 6.88 (0.5H, d,J=8.3 Hz), 7.30-7.50 (5H, m), 7.71 (0.5H, d, J=6.4 Hz), 8.79 (1H, m),9.29 (0.3H, S), 9.70 (0.7H, s); IR (KBr); υ 3380, 1642, 1599, 1499,1321, 1127, 768 cm⁻¹. Mass (FAB); m/z 487 (M+H); Elementary Analysis: AsC₃₀H₃₄N₂O₄.HCl.0.3H₂O; Calcd.: C, 68.18; H, 6.79; N, 5.30; Cl, 6.71;Found.: C, 68.06; H, 7.11; N, 5.46; Cl, 6.37.

Compound 100

mp>145° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.25 (2H, m),0.48-0.59 (2H, m), 0.79 (2.1H, t, J=7.3 Hz), 0.90 (0.9H, t, J=7.3 Hz),0.92 (1H, m), 1.20-1.48 (5H, m), 1.58 (1H, m), 1.91-2.20 (4H, m), 2.29(1H, m), 2.53 (1H, m), 2.67-2.85 (3H, m), 2.81 (2.1H, s), 3.01 (0.9H,S), 3.11 (1H, br d, J=18.6 Hz), 3.31 (1H, m), 3.45 (4.2H, br s,3.6×OH+0.6×COOH), 3.57 (1H, m), 4.06 (1.6H, s), 4.62 (0.7H, d, J=7.8Hz), 4.74 (0.3H, d, J=7.8 Hz), 6.05 (0.7H, d, J=15.1 Hz), 6.35-6.44(1.0H, m), 6.54-6.71 (2.3H, m), 9.26 (1H, br s, NH+). IR (KBr); υ 3396,1736, 1655, 1601, 1460, 1410, 1319, 1123, 1067, 1035, 922, 859 cm⁻¹.Mass (FAB); m/z 453 ((M+H)+); Elementary Analysis: AsC₂₇H₃₆N₂O₄.0.8C₄H₆O₆.1.1H₂O; Calcd.: C, 61.22; H. 7.32; N, 4.73. Found.:C, 61.13; H, 7.23; N, 4.82.

Compound 101

mp 208.0-225.0° C. (decomposition, ether); NMR (400 MHz, DMSO-d₆); (datafor 0.5 tartrate); δ 0.25 (2H, br s), 0.54 (2H, m), 0.93 (1H, m),1.27˜1.47 (3H, m), 1.66 (1H, m), 1.88˜5.20 (3H, br OH×2), 2.08˜2.19 (2H,m), 2.30 (1H, m), 2.44˜2.53 (2H, m), 2.58˜2.80 (3H, m), 2.93 (2.1H, s),3.12 (1H, m), 3.17 (0.9H, s), 3.27 (1H, br s), 4.00 (1H, s), 4.06 (0.3H,m), 4.20 (0.7H, m), 4.73 (0.7H, d, J=8.3 Hz), 4.82 (0.3H, d, J=8.3 Hz),6.55˜6.67 (2H, m), 7.19 (1.55H, d, J=7.3 Hz), 7.37 (1.55H, t, J=7.3 Hz),7.45˜7.56 (1.40H, m), 7.60 (0.5H, d, J=6.8 Hz), 9.15 (1H, br s). IR(KBr); (Data for free base); υ 3218, 2218, 1618, 1458 cm⁻¹. Mass (FAB);m/z 485 (M+H)+. Elementary Analysis: As C₃₀H₃₃N₂O₄Cl.0.7H₂O; Calcd.: C,67.52; H, 6.50; N, 5.25; Cl, 6.64. Found.: C, 67.43; H, 6.65; N, 5.25;Cl, 6.67.

Compound 102

mp 145-153° C.; NMR (400 MHz, DMSO-d₆); δ 0.20-0.32 (2H, m), 0.46-0.62(2H, m), 0.88-1.00 (1H, m), 1.20-1.50 (3H, m), 1.55-1.65 (1H, m),2.00-2.40 (3H, m), 2.42-2.60 (2H, m), 2.70-2.88 (3H, m), 2.90 (2.1H, s),3.15 (0.9H, m), 3.05-4.00 (7H, m), 4.11 (2H, S), 4.71 (0.7H, d, J=8.1Hz), 4.81 (0.3H, d, J=8.1 Hz), 6.58-6.68 (3H, m), 7.14-7.68 (5H, m),9.15 (0.3H, br s), 9.45 (0.7H, br s); IR (KBr); υ 3320, 1731, 1647,1586, 1412, 1311, 1270, 1127, 1077, 1033, 980, 859, 789, 677 cm⁻¹. Mass(FAB); m/z 505 ((M+H)+). Elementary Analysis: As C₃₀H₃₃N₂O₄F.C₄H₆O₆.H₂O;Calcd.: C, 60.71; H, 6.14; N, 4.16; F, 2.82. Found.: C, 60.63; H, 6.22;N, 4.07; F, 2.81.

Compound 103

mp>161° C. (decomposition); NMR (400 MHz, DMSO-d₆); 0.17-0.27 (2H, m),0.45-0.58 (2H, m), 0.89(1H, m), 1.16-1.44 (3H, m), 1.50-1.61 (1H, m),2.02-2.18 (2H, m), 2.28 (1H, m), 2.43 (1H, m), 2.53-2.78 (3H, m), 2.81(1.68H, s), 2.93 (0.18H, s), 2.98 (0.72H, s), 3.04 (1H, br d, J=19.1Hz), 3.10 (0.42H, s), 3.17-3.28 (1H, m), 3.35 (1H, m), 3.50 (3H, br s,3×OH), 3.98-4.37 (1.4H, m), 4.04 (1H, s), 4.67 (0.8H, d, J=7.8 Hz), 4.76(0.14H, d, J=8.3 Hz), 4.77 (0.06H, d, J=8.3 Hz), 5.62 (0.06H, s), 6.12(0.24H, s), 6.52 (0.56H, d, J=8.3 Hz), 6.52-6.78 (0.88H, m), 6.61(0.56H, d, J=8.3 Hz), 7.41-7.96 (5H, m), 9.02-9.60 (1H, m, NH+), 15.50(0.06H, s), 15.76 (0.24H, s). IR (KBr); υ 3390, 1686, 1626, 1452, 1323,1278, 1125, 1035, 926, 859 cm⁻¹. Mass (FAB); m/z 503 ((M+H)+);Elementary Analysis: As C₃₀H₃₄N₂O₅.0.5C₄H₆O₆.1.2H₂O; Calcd.: C, 64.14;H, 6.63; N, 4.67. Found.: C, 64.20; H, 6.57; N, 4.61.

Compound 104

mp 161-164° C; NMR (400 MHz, DMSO-d₆); δ 0.18-0.30 (2H, m), 0.46-0.60(2H, m), 0.85-0.97 (1H, m), 1.22-1.50 (3H, m), 1.53-1.62 (1H, m),2.03-2.21 (2H, m), 2.23-2.35 (1H, m), 2.50-2.90 (4H, m), 2.91 (2.1H, s),3.18 (0.9H, s), 3.10-4.20 (3H, m), 4.05 (1H, s), 4.67 (0.7H, d, J=8.3Hz), 4.81 (0.3H, d, J=8.3 Hz), 6.58 (0.3H, d, J=7.8 Hz), 6.63 (1H, d,J=7.8 Hz), 6.73 (0.7H, d, J=7.8 Hz), 6.84 (0.7H, d, J=15.6 Hz), 7.42(0.3H, d, J=15.9 Hz), 7.45 (0.7H, d, J=15.6 Hz), 7.57 (0.3H, d, J=15.6Hz), 7.66 (0.7H, dd, J=8.3, 7.8 Hz), 7.71 (0.3H, dd, 8.3, 7.8 Hz), 7.93(0.7H, d, J=7.8 Hz), 8.15-8.27 (2H, m), 8.60 (0.3H, s), 9.12 (0.3H, brs), 9.28 (0.7H, br s). IR (KBr); υ 3380, 1649, 1601, 1531, 1352, 1127,1035, 922, 859, 810, 743 cm¹. Mass (FAB); m/z 532 ((M+H)+). ElementaryAnalysis: As C₃₀H₃₃N₃O₆.0.5C₄H₆O₆.2.2H₂O; Calcd.: C, 59.47; H, 6.30; N,6.50. Found.: C, 59.42; H, 5.96; N, 6.25.

Example 9517-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3,4-difluorophenylacetamido)morphinan.hydrochloride105

128 mg of 3,4-difluorophenylacetic acid and 131 mg of carbonyldiimidazole were dissolved in 2.5 ml of anhydrous tetrahydrofuran. Afterrefluxing while heating for 30 minutes, the solution was cooled to roomtemperature. A solution of 200 mg of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan4 dissolved in 13 ml of anhydrous tetrahydrofuran was added to thereaction solution followed by refluxing while heating for 1 hour. Aftercooling to room temperature, the reaction solution was concentrated andthe resulting residue was dissolved in 16 ml of methanol and stirred for1 hour following the addition of 1 ml of 1 N aqueous sodium hydroxide.The reaction system was then concentrated followed by the addition of 40ml of ethylacetate to the residue and sequential washing with 25 ml ofwater and 25 ml of saturated brine. After drying with anhydrous sodiumsulfate, the organic layer was concentrated to obtain 439 mg of crudeproduct. This was then recrystallized from ethylacetate to obtain 190 mgof the free base of the target compound. The mother liquor was thenpurified with silica gel column chromatography (25 gchloroform/methanol=19/1) to obtain 177 mg of the free base of thetarget compound. The free base obtained in this manner was thendissolved in a mixed solvent of chloroform and methanol, and thissolution was concentrated after adding methanol solution ofhydrochloride to adjust to pH 4. The residue was re-precipitated withether and filtered to obtain 176 mg of the target compound (yield: 57%).

mp 194-208° C. (decomposition, diethylether); NMR (400 MHz, DMSO-d₆); δ0.31-0.43 (1H, m), 0.43-0.53 (1H, m), 0.53-0.64 (1H, m), 0.64-0.76 (1H,m), 0.99-1.12 (1H, m), 1.12-1.28 (1H, m), 1.28-1.45 (1H, m), 1.45-1.67(2H, m), 1.86-2.03 (1H, m), 2.35-2.50 (1H, m), 2.59-2.77 (1H, m), 2.80(0.6H, s), 2.88-3.18 (3H, m), 2.96 (2.4H, s), 3.18-3.39 (2H, m), 3.78(1.6H, s), 3.88 (0.4H, s), 3.91 (1H, d, J=6.8 Hz), 4.49 (0.2H, m), 4.62(1H, d, J=3.4 Hz), 4.97 (0.8H, dt, J=14.2, 3.4 Hz), 6.25 (0.8H, br s),6.56 (0.2H, br s), 6.58 (1H, d, J=7.8 Hz), 6.73 (1H, d, J=7.8 Hz),7.03-7.18 (1H, m), 7.25-7.45 (2H, m), 8.82 (1H, br s), 9.32 (1H, s); IR(KBr); υ 1620, 1560, 1520, 1460, 1278, 1172, 1120, 1036, 774 cm⁻¹. Mass(FAB); m/z 511 ((M+H)+). Elementary Analysis: AsC₂₉H₃₃N₂O₄ClF₂.0.7H₂O.0.25AcOEt; Calcd.: C, 61.95; H. 6.31; N, 4.82; Cl,6.09; F, 6.53; Found.: C, 61.91; H, 6.47; N, 4.81; Cl, 6.04; F, 6.53.

Examples 96-98

17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-4-benzo[b]thienylacetamido)morphinan.hydrochloride106 (yield: 74%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-benzo[b]thienylacetamido)morphinan.hydrochloride107 (yield: 71%) and17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-trifluoromethylphenylacetamido)morphinan.hydrochloride 108 (yield: 78%) were obtained by following theprocedure of example 95 but using 4-benzo[b]thienylacetic acid,3-benzo[b]thienylacetic acid and 3-trifluoromethylphenylacetic acidinstead of 3,4-difluorophenylacetic acid.

Compound 106

mp 207.0-215.0° C. (decomposition, diethylether); NMR (400 MHz,DMSO-d₆); δ 0.31-0.42 (1H, m), 0.42-0.53 (1H, m), 0.53-0.65 (1H, m),0.65-0.74 (1H, m), 1.00-1.11 (1H, m), 1.11-1.29 (1H, m), 1.29-1.48 (1H,m), 1.55 (1H, dd, J=15.1, 9.3 Hz), 1.61 (1H, br d, J=12.2 Hz), 1.88-2.00(1H, m), 2.42 (1H, dq, J=13.2, 4.9 Hz), 2.60-2.75 (1H, m), 2.81 (0.6H,s), 2.89-2.99 (1H, m), 3.02 (2.4H, s), 3.01-3.15 (2H, m), 3.19-3.32 (2H,m), 3.90 (1H, d, J=6.7 Hz), 4.11 (1.6H, s), 4.20 (0.4H, s), 4.51 (0.2H,br s), 4.63 (0.8H, d, J=3.9 Hz), 4.66 (0.2H, br s), 5.00 (0.8H, dt,J=13.7, 3.4 Hz), 6.22 (0.8H, br s), 6.49 (0.2H, br s), 6.58 (1H, d,J=8.3 Hz), 6.74 (1H, d, J=8.3 Hz), 7.22 (1H, d, J=6.8 Hz), 7.36 (0.8H,t, J=7.6 Hz), 7.35-7.40 (0.2H, m), 7.52 (0.8H, d, J=4.9 Hz), 7.64 (0.2H,d, J=5.9 Hz), 7.76 (0.8H, d, J=5.4 Hz), 7.77 (0.2H, d, J=5.9 Hz), 7.90(0.8H, d, J=8.3 Hz), 7.92 (0.2H, m), 8.82 (1H, br s), 9.29 (0.2H, s),9.32 (0.8H, s); IR (KBr); υ 1620, 1543, 1508, 1460, 1321, 1120, 1036,764 cm⁻¹. Mass (FAB); m/z 531 ((M+H)+); Elementary Analysis: AsC₃₁H₃₅N₂O₄ClS.0.7H₂O; Calcd.: C, 64.22; H, 6.33; N, 4.83; Cl, 6.12; S,5.53; Found.: C, 64.13; H, 6.43; N, 4.79; Cl, 6.43; S, 5.24.

Compound 107

mp 239-250° C. (decomposition, ethylacetate); NMR (400 MHz, DMSO-d₆); δ0.31-0.43 (1H, m), 0.43-0.53 (1H, m), 0.53-0.63 (1H, m), 0.63-0.74 (1H,m), 0.98-1.12 (1H, m), 1.12-1.31 (1H, m), 1.31-1.47 (1H, m), 1.47-1.69(2H, m), 1.82-2.07 (1H, m), 2.29-2.49 (1H, m), 2.59-2.77 (1H, m), 2.81(0.6H, s), 2.84-2.98 (1H, m), 3.03 (2.4H, s), 2.98-3.18 (2H, m),3.18-3.42 (2H, m), 3.81-3.96 (1H, m), 4.00 (1.6H, s), 4.02-4.27 (0.4H,m), 4.32-4.43 (0.2H, m), 4.66 (0.8H, d, J=3.4 Hz), 4.66-4.74 (0.2H, m),5.00 (1H, dt, J=14.2, 3.3 Hz), 6.22 (0.8H, brs), 6.59 (1H, d, J=7.8 Hz),6.73 (1H, d, J=8.3 Hz), 7.31-7.48 (2H, m), 7.52 (0.8H, s), 7.64 (0.2H,brs), 7.81 (0.8H, d, J=7.3 Hz), 7.91-8.04 (1.2H, m), 8.81 (1H, br s),9.28 (0.2H, s), 9.33 (0.8H, s); IR (KBr); υ 1620, 1510, 1460, 1321,1120, 1038 cm⁻¹. Mass (FAB); m/z 531 ((M+H)+). Elementary Analysis: AsC₃₁H₃₅N₂O₄ClS.0.5H₂O; Calcd.: C, 64.62; H, 6.29; N, 4.86; Cl, 6.15; S,5.57; Found.: C, 64.62; H, 6.50; N, 5.00; Cl, 6.08; S, 5.62.

Compound 108

mp 192.0-200.0° C. (decomposition, ethylacetate); NMR (400 MHz,DMSO-d₆); δ 0.31-0.42 (1H, m), 0.42-0.53 (1H, m), 0.53-0.62 (1H, m),0.62-0.77 (1H, m), 0.96-1.12 (1H, m), 1.12-1.31 (1H, m), 1.31-1.47 (1H,m), 1.47-1.69 (2H, m), 1.82-2.04 (1H, m), 2.30-2.49 (1H, m), 2.59-2.78(1H, m), 2.81 (0.4H, s), 2.86-3.18 (3H, m), 2.99 (2.6H, s), 3.18-3.40(2H, m), 3.90 (2H, s), 3.90-4.1 (1H, m), 4.53 (0.2H, m), 4.62 (0.8H, d,J=3.9 Hz), 4.77 (0.2H, br s), 4.98 (0.8H, dt, J=13.7, 3.9 Hz), 6.24 (1H,br s), 6.58 (1H, d, J=7.8 Hz), 6.74 (1H, d, J=8.3 Hz), 7.49-7.68 (4H,m), 8.82 (1H, br s), 9.33 (1H, s) IR (KBr); υ 1620, 1508, 1460, 1334,1166, 1120, 1077, 1036, 801, 702 cm⁻¹. Mass (FAB); m/z 543 ((M+H)+).Elementary Analysis: As C₃₀H₃₄N₂O₄ClF₃.0.5H₂O; Calcd.: C, 61.27; H,6.00; N, 4.76; Cl, 6.02; F, 9.69; Found.: C, 61.37; H, 6.08; N, 4.75;Cl, 5.89; F, 9.92.

Examples 99-110

17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-4-chlorophenylacetamido)morphinan.hydrochloride109 (yield: 78%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-chlorophenylacetamido)morphinan.hydrochloride 110 (yield: 84%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-1-naphthylacetamido)morphinan.hydrochloride111 (yield: 61%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-2-naphthylacetamido)morphinan.hydrochloride112 (yield: 63%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-thienylacetamido)morphinan.hydrochloride113 (yield: 61%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3,4-methylenedioxyphenylacetamido)morphinan.hydrochloride114 (yield: 45%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-benzo[b]thienylacetamido)morphinan.hydrochloride 115 (yield: 55%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-trifluoromethylphenylacetamido)morphinan.hydrochloride116 (yield: 57%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-9-fluorenamido)morphinan.hydrochloride117 (yield: 65%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-2,3,4,5,6-pentafluorophenylacetamido)morphinan.hydrochloride118 (yield: 68%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-3-(5-chlorobenzo[b]thienyl)acetamido]morphinan.hydrochloride119 (yield: 83%) and17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-4-benzo[b]thienylacetamido)morphinan.hydrochloride120 (yield: 76%) were obtained by following the procedure of example 95but using17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-methylaminomorphinan10 instead of the starting material of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan4, and using 4-chlorophenylacetic acid, 3=chlorophenylacetic acid,1-naphthylacetic acid, 2-naphthylacetic acid, 3-thienylacetic acid,3,4-methylenedioxyphenylacetic acid, 3-benzo[b]thienylacetic acid,3-trifluoromethylphenylacetic acid, 9-fluorenecarboxylic acid,2,3,4,5,6-pentafluorophenylacetic acid, 3-(5-chlorobenzo[b]thienyl)acetic acid and 4-benzo[b]thienylacetic acid instead of3,4-difluorophenylacetic acid.

Compound 109

mp 201.0-205.0° C. (decomposition, methanol) NMR (400 MHz, CD₃OD); δ0.31-0.58 (2H, m), 0.61-0.75 (1H, m), 0.75-0.87 (1H, m), 0.87-1.00 (1H,m), 1.00-1.12 (1H, m), 1.12-1.27 (1H, m), 1.35-1.82 (3H, m), 2.06 (1H,dq, J=13.4, 2.7 Hz), 2.42-2.73 (2H, m), 2.73-2.88 (1H, m), 2.92(2.5H,s), 3.07 (0.5H, s), 2.97-3.20 (3H, m), 3.68 (2H, dd, J=28.8, 15.6Hz), 3.51-4.38 (2H, m), 4.75 (1H, d, J=8.3 Hz), 6.82 (2H, d, J=8.8 Hz),6.87 (1H, d, J=7.8 Hz), 7.18 (2H, d, J=8.8 Hz), 7.22 (1H, m) IR (KBr); υ1626, 1493, 1460, 1321, 1125, 1035, 924, 808 cm⁻¹. Mass (FAB); m/z 509((M+H)+). Elementary Analysis: As C₂₉H₃₄N₂O₄Cl₃.0.6H₂O; Calcd.: C,62.61; H, 6.38; N, 5.04; Cl, 12.74; Found.: C, 62.56; H, 6.49; N, 5.02;Cl, 12.64.

Compound 110

mp 200.0-209.0° C. (decomposition, methanol); NMR (400 MHz, CD₃OD); δ0.31-0.58 (2H, m), 0.61-0.75 (1H, m), 0.75-0.89 (2H, m), 0.96-1.24 (2H,m), 1.34-1.82 (3H, m), 2.03 (1H, dq, J=13.2, 2.9 Hz), 2.42-2.73 (2H, m),2.73-2.88 (1H, m), 2.91 (2.5H, s), 3.09 (0.5H, s), 2.97-3.20 (3H, m),3.54-3.65 (1H, m), 3.68 (2H, s), 3.73-4.97 (1H, m), 4.75 (1H, d, J=8.3Hz), 6.62-7.39 (6H, m); IR (KBr); υ 1620, 1502, 1460, 1321, 1125, 1035,924, 808 cm⁻¹. Mass (FAB); m/z 509 ((M+H)+). Elementary Analysis: AsC₂₉H₃₄N₂O₄Cl₃.0.3H₂O; Calcd.: C, 63.22; H. 6.33; N, 5.08; Cl, 12.87;Found.: C, 63.20; H, 6.50; N, 5.03; Cl, 12.69.

Compound 111

mp 210.0-215.0° C. (decomposition, diethylether); NMR (400 MHz, CD₃OD);δ 0.31-0.60 (3H, m), 0.61-0.91 (3H, m), 0.91-1.18 (1H, m), 1.31 (1H,brd, J=14.2 Hz), 1.43-1.81 (2H, m), 1.89 (1H, dq, J=13.2, 2.9 Hz),2.42-2.73 (2H, m), 2.73-3.00 (2H, m), 2.92 (2.6H, s), 3.15 (0.4H, s),3.00-3.19 (2H, m), 3.54-3.85 (2H, m), 3.99 (1H, d, J=16.1 Hz), 4.23 (1H,d, J=16.1 Hz), 4.75 (1H, d, J=8.3 Hz), 6.80 (1H, d, J=8.30 Hz), 6.90(1H, d, J=7.82 Hz), 7.00 (1H, d, J=6.84 Hz), 7.27 (1H, t, J=7.6 Hz),7.31-7.59 (2H, m), 7.70 (2H, t, J=8.30 Hz), 7.80 (1H, d, J=8.3 Hz); IR(KBr); υ 1620, 1510, 1502, 1460, 1402, 1321, 1125, 1035, 924, 797 cm⁻¹.Mass (FAB); m/z 525 ((M+H)+).

Elementary Analysis: As C₃₃H₃₇N₂O₄Cl.0.3H₂O; Calcd.: C, 69.96; H, 6.69;N, 4.94; Cl, 6.26; Found.: C, 70.04; H, 6.68; N, 5.03; Cl, 6.20.

Compound 112

mp 207.0-214.0° C. (decomposition, diethylether); NMR (400 MHz, CD₃OD);δ 0.35-0.58 (3H, m), 0.61-0.91 (3H, m), 0.91-1.18 (1H, m), 1.23 (1H,brd, J=14.2 Hz), 1.39-1.81 (2H, m), 1.89 (1H, dq, J=13.2, 2.9 Hz),2.42-2.76 (2H, m), 2.76-3.02 (2H, m), 2.92 (2.6H, s), 3.10 (0.4H, s),3.02-3.20 (2H, m), 3.60-3.82 (2H, m), 3.86 (1H, d, J=21.5 Hz), 3.95 (1H,d, J=18.1 Hz), 4.75 (1H, d, J=8.3 Hz), 6.87-7.00 (2H, m), 7.00-7.13 (2H,m), 7.35-7.49 (2H, m), 7.49-7.58 (1H, m), 7.70 (1H, d, J=8.3 Hz),7.73-7.80 (1H, m); IR (KBr); υ 1620, 1504, 1460, 1408, 1321, 1125, 1035,859, 803, 748 cm⁻¹. Mass (FAB); m/z 525 ((M+H)+). Elementary Analysis:As C₃₃H₃₇N₂O₄Cl; Calcd.: C, 70.64; H, 6.65; N, 4.99; Cl, 6.32Found.: C,70.39; H, 6.75; N, 5.05; Cl, 6.00.

Compound 113

mp 208.0-219.0° C. (decomposition, diethylether); NMR (400 MHz,DMSO-d₆); δ 0.31-0.45 (1H, m), 0.45-0.53 (1H, m), 0.53-0,63 (1H, m),0.63-0.78 (1H, m), 0.84-1.30 (3H, m), 1.30-1.80 (2H, m), 1.90-2.14 (1H,m), 2.30-2.61 (3H, m), 2.83 (2.4H, S), 3.00 (0.6H, s), 2.75-2.91 (1H,m), 2.91-3.17 (3H, m), 3.40-3.57 (2H, m), 3.57-3.72 (1H, m), 3.72-3.88(1H, m), 4.81 (0.8H, d, J=8.3 Hz), 4.87 (0.2H, d, J=8.3 Hz), 6.30 (0.2H,s), 6.40 (0.8H, s), 6.62 (1H, d, J=4.9 Hz), 6.72 (1H, s), 6.73 (1H, d,J=8.3 Hz), 6.82 (1H, d, J=8.3 Hz), 7.38 (0.8H, dd, J=4.9, 2.9 Hz), 7.47(0.2H, dd, J=4.9, 2.9 Hz), 8.80 (1H, br s), 9.28 (0.2H, s), 9.65 (0.8H,s); IR (KBr); υ 1620, 1508, 1460, 1321, 1125, 1035, 922, 859 cm⁻¹. Mass(FAB); m/Z 481 ((M+H)+). Elementary Analysis: As C₂₇H₃₃N₂O₄ClS.0.5H₂O;Calcd.: C, 61.64; H, 6.51; N, 5.32; Cl, 6.74; S, 6.10; Found.: C, 61.77;H, 6.50; N, 5.19; Cl, 6.65; S, 5.83.

Compound 114

mp 203.0-208.0° C. (decomposition, ethylacetate, diethylether); NMR (400MHz, DMSO-d₆); δ 0.31-0.45 (1H, m), 0.45-0.54 (1H, m), 0.54-0.63 (1H,m), 0.63-0.73 (1H, m), 0.85-0.99 (1H, m), 0.99-1.10 (1H, m), 1.10-1.29(1H, m), 1.32-1.80 (3H, m), 1.92-2.13 (1H, m), 2.36-2.55 (2H, m),2.72-2.92 (1H, m), 2.82 (2.4H, s), 2.99 (0.6H, s), 2.92-3.13 (2H, m),3.25-3.41 (1H, m), 3.44 (2H, s), 3.48-3.70 (1H, m), 3.82 (1H, br d,J=4.9 Hz), 4.81 (0.8H, d, J=8.3 Hz), 4.87 (0.2H, d, J=8.3 Hz), 5.93(1.6H, d, J=0.98 Hz), 5.98 (0.4H, s), 6.23 (1H, dd, J=1.3, 8.1 Hz), 6.34(1H, s), 6.40 (1H, br s), 6.58-6.90 (3H, m), 8.80 (1H, brs), 9.26 (0.2H,s), 9.63 (0.8H, s); IR (KBr); υ 1620, 1504, 1491, 1323, 1249, 1125, 1036cm⁻¹. Mass (FAB); m/z 519 ((M+H)+). Elementary Analysis: AsC₃₀H₃₅N₂O₆Cl.0.4H₂O; Calcd.: C, 64.08; H, 6.41; N, 4.98; Cl, 6.31;Found.: C, 64.00; H, 6.43; N, 5.01; Cl, 6.27.

Compound 115

mp 215.0-225.0° C. (decomposition, ethylacetate, diethylether); NMR (400MHz, DMSO-d₆); δ 0.31-0.45 (1H, m), 0.45-0.53 (1H, m), 0.53-0.62 (1H,m), 0.62-0.73 (1H, m), 0.79-0.89 (1H, m), 0.89-1.12 (2H, m), 1.34-1.60(2H, n), 1.98-2.07 (1H, m), 2.39-2.55 (2H, m), 2.73-2.98 (1H, m), 2.85(2.4H, s), 3.07 (0.6H, s), 2.98-3.13 (2H, m), 3.17-3.39 (2H, m),3.50-3.61 (1H, m), 3.68 (1H, d, J=16.1 Hz), 3.78 (1H, br d, J=3.9 Hz),3.88 (1H, d, J=16.1 Hz), 4.83 (0.8H, d, J=8.3 Hz), 4.90 (0.2H, d, J=8.3Hz), 6.29 (0.2H, s), 6.35 (0.8H, s), 6.03 (0.2H, d, J=8.3 Hz), 6.70(0.2H, d, J=8.3 Hz), 6.74 (0.8H, d, J=8.3 Hz), 6.82 (0.8H, d, J=8.3 Hz),7.08 (0.8H, s), 7.21-7.42 (2.8H, m), 7.48 (0.2H, s), 7.77-7.82 (0.2H,m), 7.92 (0.8H, d, J=7.8 Hz), 7.97-8.02 (0.2H, m), 8.78 (1H, br s), 9.28(0.2H, s), 9.68 (0.8H, s); IR (KBr); υ 1626, 1502, 1460, 1319, 1125,1035 cm¹. Mass (FAB); m/z 531 ((M+H)+). Elementary Analysis: AsC₃₁H₃₅N₂O₄ClS.0.4H₂O; Calcd.: C, 64.83; H, 6.28; N, 4.88; Cl, 6.17; S,5.58; Found.: C, 64.85; H, 6.42; N, 4.89; Cl, 6.15; S, 5.53.

Compound 116

mp 195.0-203.0° C. (decomposition, methanol); NMR (400 MHz, DMSO-d₆); δ0.31-0.45 (1H, m), 0.45-0.53 (1H, m), 0.53-0.63 (1H, m), 0.63-0.77 (1H,m), 0.96-1.12 (2H, m), 1.12-1.30 (1H, m), 1.30-1.80 (3H, m), 2.06 (1H,br q, J=13.2 Hz), 2.39-2.59 (2H, m), 2.85 (2.4H, s), 3.05 (0.6H, s),2.71-2.92 (1H, m), 2.92-3.12 (2H, m), 3.41-3.58 (1H, m), 3.68 (1H, d,J=3.4 Hz), 3.58-3.77 (1H, m), 3.77-4.10 (2H, m), 4.84 (0.8H, br d, J=5.4Hz), 4.88 (0.2H, br d, J=5.4 Hz), 6.30 (0.2H, br s), 6.42 (0.8H, br s),6.62 (0.2H, d, J=8.3 Hz), 6.69 (0.2H, d, J=8.3 Hz), 6.72 (0.8H, d, J8.3Hz), 6.81 (0.8H, d, J=8.3 Hz), 7.13 (0.8H, s), 7.17 (0.2H, d, J=6.8 Hz),7.22-7.28 (0.2H, m), 7.30 (0.8H, d, J=7.8 Hz), 7.48 (1H, t, J=7.8 Hz),7.52-7.63 (1H, m), 8.80 (1H, br s), 9.25 (0.2H, s), 9.64 (0.8H, s); IR(KBr); υ 1628, 1508, 1460, 1334, 1166, 1127, 1077, 1035, 922, 704 cm¹.Mass (FAB); m/z 543 ((M+H)+); Elementary Analysis: As C₃₀H₃₄N₂O₄ClF₃;Calcd.: C, 62.23; H, 5.92; N, 4.84; Cl, 6.12; F, 9.84; Found.: C, 62.19;H, 6.04; N, 4.82; Cl, 5.76; F, 9.87.

Compound 117

mp 215.0-224.0° C. (decomposition, ethylacetate); NMR (400 MHz,DMSO-d₆); δ 0.31-0.47 (1H, m), 0.47-0.57 (1H, m), 0.57-0.64 (1H, m),0.64-0.77 (1H, m), 0.98-1.13 (1H, m), 1.20-1.60 (2H, m), 1.60-1.92 (2H,m), 2.31-2.70 (2H, m), 2.79-2.91 (1H, m), 2.97 (2.1H, s), 2.99-3.15 (2H,m), 3.36 (0.9H, s), 3.37-3.60 (2H, m), 3.81 (0.3H, br d, J=5.2 Hz), 3.89(0.7H, br d, J=5.2 Hz), 3.72-3.93 (0.3H, m), 4.12-4.29 (0.7H, m),4.90-5.02 (0.3H, m), 5.04 (0.7H, d, J=7.3 Hz), 5.09 (0.7H, s), 5.38(0.3H, m), 6.17 (0.3H, br s), 6.46 (0.7H, br s), 6.61 (1H, s), 6.55-6.78(1H, m), 7.08-7.52 (6H, m), 7.64 (1H, d, J=7.3 Hz), 7.84 (1H, dd, J=7.8,4.4 Hz), 7.91 (1H, d, J=7.3 Hz), 8.77 (0.3H, br s), 8.83 (0.7H, br s),9.24 (0.3H, s), 9.26 (0.7H, s); IR (KBr); υ 1620, 1510, 1460, 748 cm⁻¹.Mass (FAB); m/z 549 ((M+H)+). Elementary Analysis: AsC₃₅H₃₇N₂O₄Cl.0.6H₂O; Calcd.: C, 70.54; H, 6.46; N, 4.70; Cl, 5.95;Found.: C, 70.77; H, 6.54; N, 4.71; Cl, 5.58.

Compound 118

mp 208.0-214.0° C. (decomposition, methanol); NMR (400 MHz, DMSO-d₆); δ0.31-0.47 (1H, m), 0.47-0.56 (1H, m), 0.56-0.63 (1H, m), 0.63-0.77 (1H,m), 1.00-1.13 (1H, m), 1.20-1.65 (3H, m), 1.74 (1H, br t, J=13.4 Hz),2.16 (1H, br q, J=12.7 Hz), 2.39-2.62 (2H, m), 2.89 (2.4H, s), 2.76-2.96(1H, m), 2.96-3.12 (2H, m), 3.17 (0.6H, s), 3.20-3.45 (2H, m), 3.62-3.75(1H, m), 3.75-3.98 (3H, m), 4.85 (0.8H, d, J=7.8 Hz), 4.94 (0.2H, d,J=7.8 Hz), 6.38 (0.2H, br s), 6.52 (0.8H, brs), 6.62 (0.2H, d, J=8.3Hz), 6.68 (1H, d, J=8.3 Hz), 6.74 (0.8H, d, J=7.8 Hz), 8.85 (1H, br s),9.27 (0.2H, S), 9.41 (0.8H, s); IR (KBr); υ 1638, 1510, 1315, 1127,1009, 919, 859 cm⁻¹. Mass (FAB); m/z 565 ((M+H)+). Elementary Analysis:As C₂₉H₃₀N₂O₄ClF₅.0.2H₂O; Calcd.: C, 57.61; H, 5.07; N, 4.63; Cl, 5.86;F, 15.71; Found.: C, 57.60; H, 5.36; N, 4.74; Cl, 5.94; F, 15.51.

Compound 119

mp 210.0-219.0° C. (decomposition, diethylether); NMR (400 MHz,DMSO-d₆); δ 0.31-0.45 (1H, m), 0.45-0.54 (1H, ni), 0.54-0.62 (1H, m),0.62-0.73 (1H, m), 1.00-1.12 (1H, m), 1.19-1.57 (3H, m), 1.61-1.78 (1H,m), 2.00-2.18 (1H, m), 2.40-2.60 (2H, m), 2.73-2.92 (1H, m), 2.87 (2.4H,s), 3.09 (0.6H, s), 2.92-3.13 (2H, m), 3.23-3.41 (2H, m), 3.59-3.69(0.8H, m), 3.76 (0.8H, d, J=16.5 Hz), 3.80-3.90 (1H, m), 3.89 (0.8H, d,J=16.5 Hz), 3.95 (0.4H, s), 4.00-4.12 (0.2H, m), 4.88 (0.8H, d, J=7.9Hz), 4.90 (0.2H, d, J=7.9 Hz), 6.35 (0.2H, br s), 6.47 (0.8H, br s),6.63 (0.2H, d, J=7.9 Hz), 6.69 (1H, d, J=8.5 Hz), 6.78 (0.8H, d, J=7.9Hz), 7.23 (0.8H, s), 7.36 (0.8H, dd, J=8.6, 1.8 Hz), 7.40 (0.2H, dd,J=8.6, 1.8 Hz), 7.60 (0.2H, s), 7.66 (0.8H, d, J=1.8 Hz), 7.86 (0.2H, d,J=1.8 Hz), 7.97 (0.8H, d, J=8.6 Hz), 8.01 (0.2H, d, J=8.5 Hz), 8.82 (1H,br s), 9.25 (0.2H, s), 9.60 (0.8H, s); IR (KBr); υ 1628, 1508, 1427,1321, 1127, 1079, 1035, 859, 835 cm⁻¹. Mass (FAB); m/z 565 ((M+H)+);Elementary Analysis: As C₃₁H₃₄N₂O₄Cl₂S.0.3H₂O; Calcd.: C, 61.34; H,5.75; N, 4.62; Cl, 11.68; S, 5.28; Found.: C, 61.40; H, 5.81; N, 4.63;Cl, 11.38; S, 5.20.

Compound 120

mp 219.0-226.0° C. (decomposition, diethylether); NMR (400 MHz,DMSO-d₆); δ 0.31-0.45 (1H, m), 0.45-0.53 (1H, m), 0.53-0.62 (2H, m),0.62-0.73 (1H, m), 0.77-0.92 (1H, m), 0.97-1.12 (1H, m), 1.43 (1H, d,J=12.2 Hz), 1.47 (1H, d, J=10.3 Hz), 1.91 (1H, br q, J=13.2 Hz), 2.48(2H, d, J=8.6 Hz), 2.77-2.89 (1H, m), 2.83 (2.4H, s), 2.92 (1H, dd,J=19.5, 6.1 Hz), 3.06 (0.6H, s), 2.99-3.11 (1H, m), 3.25-3.39 (1H, m),3.51-3.61 (1H, m), 3.78 (1H, d, J=5.4 Hz), 3.85 (1H, d, J=15.4 Hz), 3.89(1H, d, J=15.4 Hz), 4.83 (0.8H, d, J=8.3 Hz), 4.91 (0.2H, d, J=8.3 Hz),6.31 (0.2H, br s), 6.37 (0.8H, br s), 6.63 (0.2H, d, J=8.3 Hz), 6.70(0.2H, dd, J=7.8, 2.0 Hz), 6.77 (0.8H, d, J=8.3 Hz), 6.80-6.90 (1.8H,m), 6.98 (1H, d, J=5.4 Hz), 7.18 (0.8H, t, J=7.8 Hz), 7.31 (0.2H, t,J=7.8 Hz), 7.36 (0.8H, s), 7.50 (0.2H, d, J=4.9 Hz), 7.60 (0.8H, d,J=5.4 Hz), 7.73 (0.2H, d, J=5.9 Hz), 7.82 (0.8H, d, J=8.3 Hz), 7.88(0.2H, d, J=7.8 Hz), 8.78 (1H, br s), 9.25 (0.2H, s), 9.66 (0.8H, s); IR(KBr); υ 1620, 1543, 1516, 1460, 1125, 1033, 766 cm⁻¹. Mass (FAB); m/z531 ((M+H)+). Elementary Analysis: As C₃₁H₃₅N₂O₄ClS.0.4H₂O; Calcd.: C,64.83; H, 6.28; N, 4.88; Cl, 6.17; S 5.58; Found.: C, 65.03; H, 6.49; N,4.78; Cl, 6.03; S, 5.19.

Examples 111-113

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(3,4-dichlorophenylacetamido)morphinan.hydrochloride121 (yield: 54%) and17-allyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan.hydrochloride122 (yield: 63%),17-allyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan.hydrochloride 123 (yield: 76%) were obtained by following theprocedure of example 95 but using17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-aminomorphinan (J. B.Jiang, R. N. Hanson, P. S. Portoghese and A. E. Takemori, J. Med. Chem.,20, 1100 (1977)),17-allyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan 12 and17-allyl-4,5α-epoxy-3,14β-dihydroxy-6β-methylaminomorphinan 1 instead ofthe starting material of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan4, and using 3,4-dichlorophenylacetic acid instead of3,4-difluorophenylacetic acid.

Compound 121

mp 245.0-254.0° C. (decomposition, methanol); NMR (400 MHz, DMSO-d₆); δ0.31-0.46 (1H, m), 0.46-0.53 (1H, m), 0.53-0.63 (1H, m), 0.63-0.75 (1H,m), 0.98-1.12 (1H, m), 1.21-1.39 (1H, m), 1.39-1.57 (2H, m), 1.57-1.80(2H, m), 2.28-2.48 (2H, m), 2.77-2.92 (1H, m), 3.02 (1H, brd, J=6.4 Hz),3.07 (1H, br d, J=5.9 Hz), 3.19-3.41 (3H, m), 3.45 (1H, d, J=14.7 Hz),3.50 (1H, d, J=14.7 Hz), 3.82 (1H, br s), 4.58 (1H, d, J=7.8 Hz), 6.17(1H, br s), 6.63 (1H, d, J=7.8 Hz), 6.71 (1H, d, J=8.3 Hz), 7.25 (1H,dd, J=8.3, 2.0 Hz), 7.53 (1H, d, J=2.0 Hz), 7.57 (1H, d, J=8.3 Hz), 8.45(1H, br s), 8.82 (1H, br s), 9.34 (1H, d, J=1.5 Hz); IR (KBr); υ 1655,1545, 1508, 1461, 1128, 1034, 922 cm⁻¹. Mass (FAB); m/z 529 ((M+H)+).Elementary Analysis: As C₂₈H₃₁N₂O₄Cl₃.0.4H₂O; Calcd.: C, 58.67; H, 5.59;N, 4.89; Cl, 18.56; Found.: C, 58.70; H, 5.65; N, 4.88; Cl, 18.63.

Compound 122

mp 214-216° C. NMR (400 MHz, DMSO-d₆); δ 1.16 (1H, m), 1.34 (1H, m),1.51 (1H, m), 1.62 (1H, m), 1.86 (1H, m), 2.41 (1H, m), 2.72 (1H, m),2.80 (0.5H, s), 2.95 (2.5H, s), 3.0-3.3 (2H, m), 3.40 (1H, m), 3.52 (1H,m), 3.88 (3H, m), 4.45 (0.2H, m), 4.61 (0.8H, d, J=3.9 Hz), 4.73 (0.2H,m), 4.95 (0.8H, m), 5.57 (2H, m), 5.89 (1H, m), 6.14 (0.8H, brs), 6.48(0.2H, brs), 6.59 (1H, d, J=8.3 Hz), 6.72 (1H, d, J=8.3 Hz), 7.23 (1H,m), 7.52 (1H, d, J=2.0 Hz), 7.58 (1H, m), 9.12 (1H, brs), 9.32 (1H, s);IR (KBr); υ 3300, 1624, 1473, 1118, 1035, 804 cm⁻¹. Mass (FAB); m/z 529(M+H); Elementary Analysis: As C₂₈H₃₀N₂O₄Cl₂.HCl.0.4H₂O; Calcd.: C,58.68; H, 5.59; N, 4.89; Cl, 18.56; Found.: C, 58.77; H, 5.66; N, 4.87;Cl, 18.29.

Compound 123

mp 185° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 1.15-1.39 (2H, m),1.44 (0.2H, brd, J=9.2 Hz), 1.51 (0.8H, brd, J=9.8 Hz), 1.61-1.68 (1H,m), 2.00-2.11 (1H, m), 2.44-2.57 (2H, m), 2.83 (2.4H, s), 2.90-3.00 (1H,m), 3.02 (0.6H, s), 3.07-3.15 (1H, m), 3.35-3.39 (0.2H, m), 3.37 (0.8H,d, J=6.7 Hz), 3.43-3.55 (2H, m), 3.57 (1.6H, d, J=3.1 Hz), 3.70-3.79(1.4H, m), 3.88-4.05 (1H, m), 4.80-4.88 (1H, m), 5.52 (1H, brd, J=11.0Hz), 5.62 (1H, d, J=7.1 Hz), 5.83-5.96 (1H, m), 6.10-6.38 (1H, m), 6.64(0.2H, d, J=8.2 Hz), 6.69 (0.2H, d, J=8.2 Hz), 6.73 (0.8H, d, J=8.2 Hz),6.80 (0.8H, d, J=8.2 Hz), 6.99 (0.8H, dd, J=8.6, 1.8 Hz), 7.10 (0.8H, d,J=1.8 Hz), 7.19-7.23 (0.2H, m), 7.47-7.50 (0.2H, m), 7.50 (0.8H, d,J=8.5 Hz), 7.55 (0.2H, d, J=8.6 Hz), 9.18 (1H, brs), 9.25 (0.2H, s),9.63 (0.8H, s). IR (KBr); υ 3380, 1620, 1502, 1475, 1321, 1125, 1033cm⁻¹. Mass (EI); m/z 528 (M+). Elementary Analysis: AsC₂₈H₃₀N₂O₄Cl₂.HCl.H₂O; Calcd.: C, 57.59; H, 5.70; N, 4.80; Cl, 18.21;Found.: C, 57.93; H, 5.80; N, 4.82; Cl, 17.85.

Example 11417-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-3-(3-trifluoromethylphenyl)propiolamido]morphinan.hydrochloride124

400 mg (1.12 mmol) of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-methylaminomorphinan10 and 360 mg (1.68 mmol) of 3-(3-trifluoromethylphenyl)propiolic acidwere dissolved in 12 ml of chloroform followed by sequential addition of0.40 ml (2.91 mmol) of N-ethylpiperidine and 428 mg (1.68 mmol) ofbis-(2-oxo-3-oxazolidinyl)phosphinic chloride and stirring for 12 hoursat room temperature. Then, 15 ml of 1 N aqueous sodium hydroxide wereadded to separate layers, and the organic layer was washed with 10 mleach of water and saturated brine, dried and concentrated. The residuewas dissolved in 10 ml of methanol followed by the addition of 2 ml of 1N aqueous sodium hydroxide and stirring for 3 hours. 30 ml ofethylacetate were then added to separate layers, and the resultingorganic layer was washed with 20 ml of saturated brine, dried andconcentrated. The residue was purified with silica gel columnchromatography (Merk 9385, 30 g, chloroform/methanol=30/1) to obtain562.8 ng of the free base of the target compound. This was thenre-precipitated from hexane and ethylacetate, and the resulting solidwas dissolved in ethylacetate. An excess amount of ethylacetate solutionof hydrochloride solution was added followed by stirring and filtrationof the resulting precipitate to obtain 274 mg of the target compound(yield: 42%).

mp>195° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.42 (1H, m), 0.52(1H, m), 0.59 (1H, m), 0.67 (1H, m), 1.07 (1H, m), 1.29-1.51 (3H, m),1.73-1.83 (1H, m), 2.09-2.26 (1H, m), 2.40-2.58 (2H, m), 2.86 (1H, m),2.98 (2.4H, s), 3.02-3.11 (2H, m), 3.31 (0.6H, s), 3.30-3.38 (2H, m),3.87 (1H, br d, J=5.9 Hz), 4.13 (1H, m), 4.89 (0.8H, d, J=8.3 Hz), 4.96(0.2H, d, J=8.3 Hz), 6.40 (0.2H, s, OH), 6.46 (0.8H, d, J=7.3 Hz), 6.53(0.8H, s, OH), 6.60 (0.8H, d, J=7.3 Hz), 6.66 (0.2H, d, J=7.3 Hz), 6.72(0.2H, d, J=7.3 Hz), 7.47 (0.8H, br s), 7.57 (0.8H, d, J=7.8 Hz), 7.63(0.8H, dd, J=7.8, 7.8 Hz), 7.73 (0.2H, dd, J=7.8, 7.8 Hz),7.83 (0.8H, d,J=7.8 Hz), 7.90 (0.2H, d, J=7.8 Hz), 7.97 (0.2H, d, J=7.8 Hz), 8.06(0.2H, br s), 8.81 (1H, m, NH+), 9.30 (0.8H, s, OH), 9.31 (0.2H, s, OH).IR (KBr); υ 3400, 2224, 1620, 1439, 1334, 1170, 1127, 1073, 1035, 924,806 cm⁻¹. Mass (FAB); m/z 553 ((M+H)+). Elementary Analysis: AsC₃₁H₃₁F₃N₂O₄.HCl.0.5H₂O; Calcd.: C, 62.26; H, 5.56; Cl, 5.93; F, 9.53;N, 4.68; Found.: C, 62.25; H, 5.64; Cl, 5.78; F, 9.49; N, 4.73.

Example 115

17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[N-methyl-3-(3-trifluoromethylphenyl)propiolamido]morphinan.hydrochloride125 was obtained by following the procedure of example 114 but using17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan4 instead of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-methylaminomorphinan10.

mp>190° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.41 (1H, m), 0.48(1H, m), 0.62 (1H, m), 0.68 (1H, m), 1.07 (1H, m), 1.14-1.33 (1H, m),1.48-1.70 (3H, m), 1.92-2.07 (1H,m), 2.47 (1H, m), 2.70 (1H, m),2.92-3.15 (3H, m), 2.93 (1.2H, s), 3.22-3.38 (2H, m), 3.26 (1.8H, s),3.96 (1H, m), 4.72 (0.6H, d, J=3.4 Hz), 4.85 (0.4H, d, J=3.4 Hz), 4.92(0.6H, ddd, J=14.2, 3.9, 3.9 Hz), 5.07 (0.4H, ddd, J=13.2, 3.9, 3.9 Hz),6.34 (0.6H, s, OH), 6.43 (0.4H, s, OH), 6.61 (0.6H, d, J=7.8 Hz), 6.61(0.4H, J=7.3 Hz), 6.75 (0.6H, d, J=7.8 Hz), 6.75 (0.4H, d, J=7.3 Hz),7.73 (0.6H, dd, J=7.8, 7.3 Hz), 7.82 (0.4H, dd, J=7.8, 7.3 Hz), 7.91(0.6H, d, J=7.3 Hz), 7.92 (0.4H, d, J=7.3 Hz), 7.98 (0.6H, d, J=7.8 Hz),8.06 (0.6H, br s), 8.06 (0.4H, d, J=7.8 Hz), 8.08 (0.4H, br s),8.82-8.94 (1H, m, NH+), 9.38 (0.4H, s, OH), 9.38 (0.6H, s, OH). IR(KBr); υ 3400, 2220, 1611, 1460, 1334, 1172, 1122, 1071, 1036, 922, 806cm⁻¹. Mass (FAB); m/z 553 ((M+H)+). Elementary Analysis: As C₃₁H₃₁F₃N₂₄.HCl.0.6H₂O; Calcd.: C, 62.07; H, 5.58; Cl, 5.91; F, 9.50; N, 4.67;Found.: C, 61.96; H, 5.64; Cl, 6.06; F, 9.47; N, 4.69.

Example 116

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan.5tartrate 126 was obtained by following the procedure of example 114 butusing17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-methylaminomorphinan4 instead of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-methylaminomorphinan10, and using 3-(4-trifluoromethylphenyl)propiolic acid instead of3-(3-trifluoromethylphenyl)propiolic acid.

mp 197.0° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.10-0.30 (2H,m), 0.44-0.63 (2H, m), 0.83-0.99 (1H, m), 1.10-1.35 (1H, m), 1.40-1.60(3H, m), 1.70-1.88 (1H, m), 2.15-2.34 (2H, m), 2.39-2.62 (2H, m),2.62-2.84 (2H, m), 2.93 (1.5H, s), 3.00-3.13 (1H, m), 3.25 (1.5H, s),3.20-3.34 (1H, m), 2.40-4.40 (3H, br s), 4.10 (1H, s), 4.62 (0.5H, br d,J=3.4 Hz), 4.70 (0.5H, br d, J=2.9 Hz), 4.85 (0.5H, ddd, J=14.2, 3.9,3.9 Hz), 5.03 (0.5H, ddd, J=13.2, 3.9, 3.9 Hz), 6.53 (1H, d, J=8.3 Hz),6.64 (0.5H, d, J=7.8 Hz), 6.65 (0.5H, d, J=8.3 Hz), 7.85 (1H, d, J=8.3Hz), 7.89 (1H, d, J=8.3 Hz), 7.90 (1H, d, J=8.3 Hz), 7.93 (1H, d, J=8.3Hz), 8.80-9.60 (1H, br s). IR (KBr); υ 3416, 2222, 1609, 1508, 1406,1325, 1125, 1067 cm⁻¹. Mass (FAB); m/z 553 ((M+H)+). ElementaryAnalysis: As C₃₁H₃₁F₃N₂O₄.0.5C₄H₆O₆.0.5H₂O; Calcd.: C, 62.26; H, 5.54;F, 8.95; N, 4.40; Found.: C, 62.14; H, 5.58; F, 8.91; N, 4.43.

Example 17

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-3-(4-trifluoromethylphenyl)propiolamido]morphinan.hydrochloride127 was obtained by following the procedure of example 114 but using3-(4-trifluoromethylphenyl)propiolic acid instead of3-(3-trifluoromethylphenyl)propiolic acid.

mp 197.0° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.35-0.46 (1H,m), 0.46-0.56 (1H, m),0.56-0.64 (1H, m), 0.64-0.75 (1H, m), 1.01-1.15(1H, m), 1.27-1.37 (0.6H, m), 1.37-1.52 (2.4H, m), 1.70-1.85 (1H, m),2.05-2.30 (1H, m), 2.36-2.62 (2H, m), 2.80-2.92 (1H, m), 2.99 (2.4H, s),3.00-3.16 (2H, m), 3.32 (0.6H, s), 3.30-3.40 (2H, m), 3.86 (1H, br d,J=4.4 Hz), 4.05-4.18 (1H, m), 4.90 (0.8H, d, J=8.3 Hz), 4.97 (0.2H, d,J=8.8 Hz), 6.43 (0.2H, s), 6.55 (0.8H, s), 6.57 (0.8H, d, J=7.8 Hz),6.66 (1H, d, J=8.3 Hz), 6.72 (0.2H, d, J=7.8 Hz), 7.43 (1.6H, d, J=7.8Hz), 7.74 (1.6H, d, J=8.3 Hz), 7.85 (0.4H, d, J=8.8 Hz), 7.89 (0.4H, d,J=8.8 Hz), 8.83 (1H, br s), 9.32 (0.2H, s), 9.35 (0.8H, s). IR (KBr); υ3416, 2224, 1618, 1508, 1408, 1325, 1172, 1127, 1067 cm⁻¹. Mass (FAB);m/z 553 ((M+H)+). Elementary Analysis: As C₃₁H₃₁F₃N₂O₄.HCl.0.6H₂O;Calcd.: C, 62.07; H. 5.58; Cl, 5.91; F. 9.50; N. 4.67; Found.: C, 62.14;H, 5.62; Cl, 5.90; F, 9.29; N, 4.62.

Example 11817-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylmethanesulfonamido)morphinan.tartrate 128

227 mg of3-tert-butyldimethylsilyloxy-17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylmethanesulfonamido)morphinan16 obtained in reference example 8 was dissolved in 4.5 ml oftetrahydrofuran followed by the addition of 0.39 ml oftetrabutylammonium fluoride and stirring for 30 minutes. 15 ml ofethylacetate and 10 ml of saturated aqueous ammonium chloride were addedto separate layers, and the aqueous layer was extracted twice with 10 mlof ethylacetate. The resulting organic layer was concentrated afterdrying with anhydrous sodium sulfate, and the residue was purified withsilica gel column chromatography (25 g chloroform/methanol=20/1) toobtain the crude compound. This was then recrystallized fromethylacetate and methanol to obtain 158 mg of the free base of thetarget compound. This was dissolved in a mixed solvent of chloroform andmethanol, completely dissolved by addition of 20.4 mg of tartaric acidand concentrated. This residue was reprecipitated from methanol andether followed by filtration to obtain 105 mg of the target compound(yield: 49%).

mp>149° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.13-0.22 (2H, m),0.47-0.58 (2H, m), 0.82-0.92 (1H, m), 0.98-1.11 (1H, m), 1.18-1.27 (1H,m), 1.35-1.48 (2H, m), 1.55-1.67 (1H, m), 2.07-2.26 (2H, m), 2.48-2.60(1H, m), 2.60-2.73 (2H, m), 2.83 (3H, s), 3.01 (1H, brd, J=8.6 Hz),2.90-4.00 (5H, m, 3×OH), 3.98-4.07 (1H, m), 4.11 (1H, s), 4.35 (1H, d,J=3.4 Hz), 4.49 (1H, d, J=13.7 Hz), 4.53 (1H, d, J=13.7 Hz), 6.49 (1H,d, J=8.3 Hz), 6.61 (1H, d, J=8.3 Hz), 7.44 (1H, dd, J=2.0, 8.3 Hz), 7.67(1H, d, J=8.3 Hz), 7.71 (1H, d, J=2.0 Hz), 9.08 (1H, brs). IR (KBr); υ3410, 1607, 1470, 1323, 1122, 1035, 959, 917 cm⁻¹; Mass (FAB); m/z 579(M+H)+. Elementary Analysis: As C₂₈H₃₂N₂O₅Cl₂S.0.65C₄H₆N₆.0.4H₂O;Calcd.: C, 53.71; H, 5.41; N, 4.09; Cl, 10.36; S, 4.69; Found.: C,53.79; H, 5.50; N, 4.12; Cl, 10.09; S, 4.58.

Example 119

17-Cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methylphenylmethanesulfonamido)morphinan.tartrate129 (yield: 87%) was obtained by following the procedure of example 118but using3-tert-butyldimethylsilyloxy-17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-phenylmethanesulfonamido)morphinan17 instead of the starting material of3-tert-butyldimethylsilyloxy-17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylmethanesulfonamido)morphinan16.

mp>147° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.13-0.22 (2H, m),0.45-0.58 (2H, m), 0.82-1.07 (2H, m), 1.09-1.19 (1H, m), 1.33-1.42 (2H,m), 1.50-1.62 (1H, m), 2.07-2.27 (2H, m), 2.40-2.72 (3H, m), 2.79 (3H,s), 2.99 (1H, brd, J=9.0 Hz), 2.95-4.15 (5H, m, 3×OH), 3.98-4.07 (1H,m), 4.10 (1H, s), 4.34 (1H, d, J=3.4 Hz), 4.40 (1H, d, J=13.9 Hz), 4.45(1H, d, J=13.9 Hz), 6.47 (1H, d, J=8.0 Hz), 6.61 (1H, d, J=8.0 Hz),7.31-7.46 (5H, m), 9.10 (1H, brs). IR (KBr); υ 3420, 1603, 1460, 1321,1122, 1069, 1036, 959, 917 cm⁻¹. Mass (FAB); m/z 511 (M+H)+. ElementaryAnalysis: As C₂₈H₃₄N₂O₅S.0.5C₄H₆N₆.H₂O; Calcd.: C, 59.67; H, 6.51; N,4.64; S, 5.31; Found.: C, 59.50; H, 6.47; N, 4.68; S, 5.21.

Example 12017-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(3-phenylpropionyloxy)morphinanan.tartrate130

148 mg of 17-cyclopropylmethyl-4,5α-epoxy-3,6α,14β-trihydroxymorphinan(N. Chatterjie, C. E. Inturrisi, H. B. Dayton and H. Blumberg, J. Med.Chem., 18, 490 (1975); H. C. Brown and S. Krishnamurthy, J. Am. Chem.Soc., 94, 7159 (1972)) was dissolved in 0.9 ml of carbon tetrachlorideand 0.3 ml of methylene chloride followed by the addition of 0.225 mldiisopropylethylamine and 26 mg of 4-dimethylaminopyridine, and thedropwise addition of 0.13 ml of 3-phenylpropionyl chloride at 0° C.After stirring for 20 hours at room temperature, 2 ml of saturatedaqueous sodium bicarbonate was added to the reaction system to separatelayers, and the aqueous layer was extracted twice with chloroform. Theorganic layer was concentrated after drying with anhydrous sodiumsulfate. The resulting residue was dissolved in a mixed solvent ofchloroform and methanol followed by the addition of 30 mg of potassiumcarbonate and stirring for 1 hour. Water was then added to the reactionmixture to separate layer, and the aqueous layer was extracted twicewith chloroform. The resulting organic layer was concentrated afterdrying with anhydrous sodium sulfate, and the residue was purified withsilica gel column chromatography (15 g chloroform/methanol=20/1) toobtain 95.3 mg of the free base of the target compound. This was thendissolved in methanol, completely dissolved by addition of 15 mg oftartaric acid and concentrated. The residue was re-precipitated fromether followed by filtration to obtain 103 mg of the target compound(yield: 43%).

mp >110° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.18-0.28 (2H,m), 0.47-0.60 (2H, m), 0.83-0.95 (1H, m), 1.19-1.28 (1H, m), 1.32-1.49(3H, m), 1.74-1.82 (1H, m), 2.19-2.29 (2H, m), 2.40-2.47 (2H, m),2.55-2.80 (6H, m), 3.08 (1H, brd, J=18.9 Hz), 3.28 (1H, brs), 3.36 (5H,m), 4.10 (2H, s), 4.64 (1H, d, J=4.9 Hz), 5.27-5.31 (1H, m), 6.51 (1H,d, J=8.2 Hz), 6.63 (1H, d, J=8.2 Hz), 7.13-7.19 (3H, m), 7.22-7.28 (2H,m), 9.10 (1H, brs). IR (KBr); υ 3400, 1719, 1460, 1307, 1267, 1122,1069, 1036 cm⁻¹. Mass (FAB); m/z 476 (M+H)+. Elementary Analysis: AsC₂₉H₃₃NO₅.0.95C₄H₆O₆.1/6C₄H₁₀O.1/6C₂H₆O.0.4H₂O; Calcd.: C, 62.91; H,6.59; N, 2.17; Found.: C, 62.92; H, 6.56; N. 2.32.

Example 12117-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[N-methyl-N′-(3,4-dichlorophenyl)ureido]morphinan.hydrochloride131

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-methylaminomorphinan4 (0.20 g) was dissolved in chloroform (5 ml) followed by the additionof 3,4-dichlorophenylisocyanate (0.26 g, 2.5 equivalents) and reactingfor 5 minutes at room temperature. The precipitated solid was filteredout and dissolved in chloroform (8 ml) and methanol (10 ml) followed bythe addition of 3 N aqueous sodium hydroxide to carry out hydrolysis for5 minutes at room temperature. The solvent was distilled off followed byaddition of saturated aqueous sodium bicarbonate (10 ml) and distilledwater (4 ml), extraction with chloroform and methanol (12/2+10/2 ml),and drying with anhydrous sodium sulfate. After purifying with silicagel column chromatography (Merk 9385, 20 g; chloroform→3%methanol/chloroform), the residue was again dissolved in chloroform andmethanol (5/0.5 ml) followed by addition of methanol solution ofhydrochloric acid to obtain the target compound (0.23 g, 70%) in theform of its hydrochloride.

mp 210° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.41 (1H, m), 0.44(1H, m), 0.62 (1H, m), 0.68 (1H, m), 1.0-1.2 (2H, m), 1.40 (1H, m), 1.60(2H, m), 1.94 (1H, m), 2.4-2.5 (1H, m), 2.68 (1H, m), 2.92 (3H, S),2.9-3.2 (3H, m), 3.3-3.4 (2H, m), 3.91 (1H, d, J=6.8 Hz), 4.74 (1H, d,J=3.9 Hz), 4.81 (1H, dt, J=13.7, 3.9 Hz), 6.34 (1H, s), 6.59 (1H, d,J=7.8 Hz), 6.73 (1H, d, J=7.8 Hz), 7.49 (1H, d, J=8.8 Hz), 7.55 (1H, dd,J=9.3, 2.4 Hz), 7.94 (1H, d, J=2.4 Hz), 8.73 (1H, s), 8.82 (1H, brs),9.32 (1H, s); IR (KBr); υ 3300, 1638, 1510, 1477, 1120, 1040 cm⁻¹. Mass(FAB); m/z 544 (M+H); Elementary Analysis: As C₂₈H₃₁N₃O₄Cl₂.HCl.0.4H₂O;Calcd.: C 57.18; H 5.62; N 7.14; Cl 18.08; Found.: C 57.32; H 5.83; N7.04; Cl 17.85.

Examples 122-124

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-N′-benzylureido)morphinan.tartrate132 (yield: 65%),17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-N′-benzylthioureido)morphinan.tartrate133 (yield: 88%) and17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-N′-benzylthioureido)morphinan.tartrate134 (yield: 74%) were obtained by following the procedure of example 121but using benzylisocyanate and benzylisothiocyanate instead of3,4-dichlorophenylisocyanate, and using17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-methylaminomorphinan10 instead of17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-methylaminomorphinan4.

Compound 132

mp 202-205° C. (decomposition, methanol-ethylacetate); NMR (400 MHz,DMSO-d₆); δ 0.28 (2H, m). 0.52 (2H, m), 0.89 (1H, m), 1.10 (1H, m), 1.24(1H, m), 1.38-1.53 (2H, m), 1.73 (1H, m), 2.15-2.30 (2H, m), 2.62-2.76(2H, m), 2.78 (3H, s), 3.04 (1H, br d, J=18.6 Hz), 3.24 (1H, m),3.39-3.52 (2H, m), 3.53 (3H, br s, 3×OH), 3.99 (1H, s), 4.28 (2H, d,J=5.9 Hz), 4.53 (1H, d, J=3.4 Hz), 4.70 (1H, m), 6.49 (1H, d, J=8.1 Hz),6.61 (1H, d, J=8.1 Hz), 6.89 (1H, t, J=5.9 Hz, NH), 7.18-7.34 (5H, m),9.03 (1H, br s, NH+). IR (KBr); υ 3422, 3204, 1630, 1615, 1589, 1535,1468, 1359, 1319, 1123, 903, 735 cm⁻¹. Mass (FAB); m/z 490 ((M+H)+);Elementary Analysis: As C₂₉H₃₅N₃O₄.0.5C₄H₆O₆; Calcd.: C, 65.94; H, 6.78;N, 7.44; Found.: C, 65.95; H, 6.74; N, 7.47.

Compound 133

mp 155-195° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.29 (2H, m),0.52 (2H, m), 0.90 (1H, m), 1.18 (1H, m), 1.35 (1H, m), 1.43 (1H, br d,J=9.1 Hz), 1.50 (1H, dd, J=14.6, 9.1 Hz), 1.77 (1H, m), 2.18-2.28 (2H,m), 2.42-2.57 (2H, m), 2.66-2.78 (2H, m), 2.95 (3H, s), 3.04 (1H, br d,J=18.9 Hz), 3.23 (1H, m), 3.48 (3H, br s, 3×OH), 4.01 (1H, s), 4.80 (1H,d, J=3.6 Hz), 4.82 (1H, dd, J=15.3, 6.1 Hz), 4.89 (1H, dd, J=15.3, 6.1Hz), 5.81 (1H, m), 6.51 (1H, d, J=7.9 Hz), 6.62 (1H, d, J=7.9 Hz), 7.23(1H, m), 7.28-7.33 (4H, m), 8.01 (1H, dd, J=6.1, 6.1 Hz, TH), 9.03 (1H,br s, NH+). IR (KBr); υ 3374, 1605, 1535, 1460, 1381, 1330, 1243, 1176,1118, 1067, 1036, 907, 698 cm⁻¹. Mass (FAB); m/z 506 ((M+H) +).Elementary Analysis: As C₂₉H₃₅N₃O₃S.0.5C₄H₆O₆.0.3H₂O.0.15CH₃COOC₂H₅;Calcd.: C, 63.33; H, 6.69; N, 7.01; S, 5.35; Found.: C, 63.44; H, 6.56;N, 6.90; S, 5.35.

Compound 134

mp 160-180° C. (decomposition).

NMR (400 MHz, DMSO-d₆); δ 0.22 (2H, m), 0.47-0.58 (2H, m), 0.91 (1H, m),1.27-1.47 (3H, m), 1.55 (1H, m), 1.94 (1H, m), 2.12 (1H, m), 2.28 (1H,m), 2.43-2.78 (5H, m), 3.07 (1H, m), 3.08 (3H, s), 3.26 (1H, m), 3.50(3.6H, br S, 3.3×OH+0.3×COOH), 4.01 (1.3H, s), 4.60 (1H, dd, J=15.3, 4.9Hz), 4.74 (1H, d, J=8.3 Hz), 4.93 (1H, dd, J=15.3, 5.9 Hz), 6.55 (1H, d,J=8.3 Hz), 6.60 (1H, d, J=8.3 Hz), 7.19-7.34 (5H, m), 7.95 (1H, dd,J=5.9, 4.9 Hz, NH), 9.11 (1H, br s, NH+). IR (KBr); υ 3352, 1721, 1605,1531, 1456, 1330, 1238, 1125, 1067, 1033, 915, 859 cm⁻¹. Mass (FAB); m/z506 ((M+H)+). Elementary Analysis: As C₂₉H₃₅N₃O₃S.0.65C₄H₆O₆.0.4H₂O;Calcd.: C, 62.18; H, 6.56; N, 6.88; S, 5.25; Found.: C, 62.09; H, 6.74;N. 6.83; S, 5.21.

Example 12517-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[N-methyl-N-2-(3,4-dichlorophenyl)ethylamino]morphinan.1.8 hydrochloride 135

234.5 mg (0.431 mmol) of17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan(free base of 1) was dissolved in 5.0 ml of anhydrous THF under argonatmosphere followed by the dropwise addition of 1.1 ml (2.2 mmol) of a2.0 M anhydrous THF solution of borane-dimethylsulfide complex at 0° C.and refluxing for 1.5 hours. This reaction solution was cooled to 0° C.followed by the addition of 2 ml of 6 N hydrochloric acid and againrefluxing for 1 hour. The reaction solution was again cooled to 0° C.and 25 ml of saturated aqueous sodium bicarbonate was added to make thesolution basic. The solution was then extracted with chloroform andmethanol (4:1) (3×20 ml), and the organic layers were combined, driedand concentrated to obtain 281 mg of an oily substance. This oilysubstance was purified with column chromatography [silica gel 25 g;chloroform-methanol (50:1→40:1)] to obtain 191.0 mg of the free base ofthe target compound. This free base was dissolved in methanol followedby the addition of a methanol solution of hydrogen chloride andconcentration. The resulting hydrochloride was purified with Sephadexgel column chromatography [methanol] to obtain 193.3 mg of the targetcompound (yield: 74%).

mp>205° C. (decomposition); NMR (400 MHz, CDCl₃; data for free base); δ0.13 (2H, m), 0.53 (2H, m), 0.85 (1H, m), 1.00 (1H, m), 1.49 (1H, dd,J=15.1, 8.8 Hz), 1.53-1.62 (2H, m), 1.71 (1H, ddd, J=15.1, 9.5, 9.5 Hz),2.0-3.1 (1H, br s, OH), 2.15-2.40 (4H, m), 2.51 (3H, s), 2.55-2.67 (2H,m, 2.72-2.85 (3H, m), 2.89 (1H, m), 2.98-3.10 (3H, m), 4.78 (1H, dd,J=3.0, 2.0 Hz), 4.98 (1H, br s, OH), 6.50 (1H, d, J=8.1 Hz), 6.68 (1H,d, J=8.1 Hz), 7.03 (1H, dd, J=8.3, 2.0 Hz), 7.28 (1H, d, J=2.0 Hz), 7.33(1H, d, J=8.3 Hz). IR (KBr); υ 3422, 1638, 1620, 1508, 1470, 1390, 1323,1241, 1172, 1122, 1035, 982, 919, 886 cm⁻¹. Mass (FAB); m/z 529((M+H)+); Elementary Analysis: As C₂₉H₃₄Cl₂N₂O₃.1.8HCl.0.4H₂O; Calcd.:C, 57.83; H; 6.12; N, 4.65; Cl, 22.37; Found.: C, 57.73; H, 6.31; N,4.60; Cl, 22.38.

Example 126

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-N-2-(3,4-dichlorophenyl)ethylaminc]morphinan.1.9hydrochloride 136 (yield: 65%) was obtained by following the procedureof example 125 but using17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3,4-dichlorophenylacetamido)morphinan(free base of 53) instead of the starting material of17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan(free base of 1).

Compound 136

mp >185° C. (decomposition); NMR (400 MHz, CDCl₃; data of free base); δ0.12 (2H, m), 0.52 (2H, m), 0.83 (1H, m), 1.29 (1H, ddd, J=13.2, 13.2,2.9 Hz), 1.44 (1H, m), 1.51 (1H, m), 1.61 (1H, ddd, J=13.2, 2.9, 2.9Hz), 1.86 (1H, m), 2.0-3.8 (2H, br s, 2×OH), 2.11 (1H, ddd, 11.7, 11.7,3.4 Hz), 2.21 (1H, ddd, J=12.2, 12.2, 4.9 HFz), 2.33-2.38 (2H, m), 2.41(3H, s), 2.47-2.56 (2H, m), 2.57-2.75 (4H, m), 2.81 (1H, m), 2.97-3.06(2H, m), 4.56 (1H, d, J=8.3 Hz), 6.56 (1H, d, J=8.1 Hz), 6.71 (1H, d,J=8.1 Hz), 7.01 (1H, dd, J=8.3, 2.0 Hz), 7.29 (1H, d, J=2.0 Hz), 7.30(1H, d, J=8.3 Hz). IR (KBr); υ 3250, 1638, 1618, 1473, 1398, 1330, 1241,1218, 1116, 1035, 982, 919, 855, 756 cm⁻¹. Mass (FAB); mp 529 ((M+H)+).Elementary Analysis: As C₂₉H₃₄Cl₂N₂O₃.1.9HCl.0.5H₂O; Calcd.: C, 57.31;H, 6.12; N, 4.61; Cl, 22.75; Found.: C, 57.40; H, 6.22; N, 4.55; Cl,22.54.

Example 127

17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-4-aminophenylacetamido)morphinanan.1.6hydrochloride 137

156.8 mg (0.282 mmol) of17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-4-nitrophenylacetamido)morphinan.hydrochloride 87 was dissolved in 2.1 ml of methanol followedby the addition of roughly 0.2 ml of a saturated methanol solution ofhydrogen chloride gas and 5.3 mg of platinum oxide, and stirring for 2.5hours at room temperature in a hydrogen atmosphere (1 atm). The reactionmixture was filtered by passing through Celite, and the filtrationresidue was washed with methanol. The filtrate and washing were combinedand concentrated to obtain 166 mg of crude product. This crude productwas purified twice with Sephadex column chromatography [methanol] toobtain 108.2 mg of the target compound (yield: 68%).

mp>220° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.39 (1H, m), 0.47(1H, m), 0.62 (1H, m), 0.69 (1H, m), 1.00-1.23 (2H, m), 1.34 (1H, m),1.45-1.63 (2H, m), 1.94 (1H, m), 2.44 (1H, m), 2.68 (1H, m), 2.78 (0.9H,s), 2.92-3.13 (3H, m), 2.93 (2.1H, s), 3.21-3.43 (2H, m), 3.67-3.82 (2H,m), 3.92-3.98 (1H, m), 4.38 (0.3H, m), 4.57 (0.3H, m), 4.61 (0.7H, d,J=3.4 Hz), 4.98 (0.7H, m), 20 6.29 (0.7H, br s, OH), 6.57 (1H, d, J=8.3Hz), 6.63 (0.3H, br s, OH), 6.72 (0.3H, d, J=8.3 Hz), 6.74 (0.7H, d,J=8.3 Hz), 6.97 (0.6H, d, J=8.3 Hz) 7.00 (1.4H, d, J=8.3 Hz), 7.16(1.4H, d, J=8.3 Hz), 7.20 (0.6H, d, J=8.3 Hz), 8.53 (2.8H, br s, NH3+),8.84 (0.8H, m, NH+), 9.30 (0.3H, br s, OH), 9.33 (0.7H, br s, OH). IR(KBr); υ 3370, 1620, 1510, 1466, 1321, 1120, 1038, 919, 804 cm⁻¹. Mass(FAB); m/z 490 ((M+H)+).

Elementary Analysis: As C₂₉H₃₅N₃O₄.1.6HCl.0.8H₂O; Calcd.: C, 61.94; H,6.85; N, 7.47; Cl, 10.09. Found.: C, 62.09; H, 7.02; N, 7.15; Cl, 9.93.

Example 128

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-aminophenylacetamido)morphinan.1.1tartrate 138 (yield: 90%) was obtained by following the procedure ofexample 127 but using17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-nitrophenylacetamido)morphinan.hydrochloride 83 instead of the starting material of17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-4-nitrophenylacetamido)morphinan.hydrochloride87.

mp>160° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.23 (2H, m), 0.53(2H, m), 0.92 (1H, m), 1.18-1.32 (2H, m), 1.48-1.53 (2H, m), 1.74 (1H,m), 2.14-2.38 (2H, m), 2.54 (1H, m), 2.63-2.84 (2H, m), 2.79 (0.9H, s),2.90 (2.1H, s), 3.08 (l1H, m), 3.26-3.41 (2H, m), 3.51-3.63 (3H, m),3.60 (7H, br s, 4×OH, NH₃+), 4.09 (0.3H, m), 4.11 (2H, s), 4.47 (0.3H,m), 4.56 (0.7H, d, J=3.4 Hz), 4.95 (0.7H, m), 6.37-6.56 (3H, m),6.58-6.64 (1H, m), 6.62-7.00 (1H, m), 9.10 (1H, br s, NH+). IR (KBr); υ3312, 1736, 1719, 1609, 1510, 1460, 1402, 1309, 1267, 1120, 1069, 1038,919, 774, 687 cm⁻¹. Mass (FAB); m/z 490 ((M+H)+). Elementary Analysis:As C₂₉H₃₅N₃O₄.1.1C₄H₆O₆.1.8H₂O. 0.5CH₃COOC₂H₅; Calcd.: C, 58.15; H,6.78; N, 5.75; Found.: C, 58.18; H, 6.76; N, 5.65.

Example 12917-Cyclopropylmethyl-3-acetoxy-4,5α-epoxy-14β-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan.hydrochloride 139

152 mg of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan.hydrochloride 1 obtained in example 11 was dissolved in 2.3 mlof pyridine followed by the addition of 0.04 ml of acetic anhydride andstirring for 30 minutes. After concentrating the reaction solvent andremoving the pyridine by azeotrope with toluene, the residue was washedwith ether to obtain 148 mg of the target compound (yield: 91%).

mp>187° C. (decomposition); NMR (400 MHz, CDCl₃); δ 0.35-0.58 (1.3H, m),0.63-0.94 (2.7H, m), 1.25-1.75 (5H, m), 2.26 (2.1H, s), 2.27 (0.9H, s),2.47-2.70 (2H, m), 2.83 (0.9H, s), 2.85 (2.1H, s), 2.90-3.26 (4H, m),3.27-3.60 (2H, m), 3.69 (1.4H, s), 3.71 (0.6H, s), 4.35-4.60 (1.3H, m),4.75-4.83 (0.3H, m), 4.86 (0.7H, d, J=2.9 Hz), 5.18-5.28 (0.7H, m), 6.70(1H, d, J=8.4 Hz), 6.72 (1H, brs), 6.87-6.93 (1H, m), 7.09 (0.7H, dd,J=8.3, 2.0 Hz), 7.30 (0.3H, dd, J=8.3, 2.0 Hz), 7.35 (0.7H, d, J=2.0Hz), 7.40 (0.7H, d, J=8.3 Hz), 7.48 (0.3H, d, J=2.0 Hz), 7.56 (0.3H, d,J=8.3 Hz), 9.40-9.70 (1H, m). IR (KBr); υ 3380, 1765, 1636, 1626, 1475,1458, 1224, 1201, 1122, 1036 cm⁻¹. Mass (FAB); m/z 585 (M+H)+.Elementary Analysis: As C₃₁H₃₄N₂O₅Cl₂.HCl; Calcd.: C, 59.86; H, 5.67; N,4.50; Cl, 17.10; Found.: C, 59.71; H, 5.70; N, 4.55; Cl, 16.95.

Examples 130-131

17-Cyclopropylmethyl-3-acetoxy-14β-hydroxy-4,5α-epoxy-6β-(N-methylcinnamamido)morphinan.tartrate140 (yield: 70%) and17-cyclopropylmethyl-3-acetoxy-14β-hydroxy-4,5α-epoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan.tartrate141 (yield: 56%) were obtained by following the procedure of example 129but using17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methylcinnamamido)morphinan.tartrate99 and17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-trifluoromethylcinnamamido)morphinan.tartrate60 instead of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan.hydrochloride1.

Compound 140

mp 142-146° C. (decomposition, ethylacetate); PNMR (400 MHz, DMSO-d₆); δ0.23 (2H, br s), 0.54 (2H, m), 0.92 (1H, m), 1.30 (1H, m), 1.38-1.50(2H, m), 1.60 (1H, m), 1.85 (1.73H, s), 2.09-2.26 (2H, m), 2.21 (1.27H,s), 2.33 (1H, m), 2.60-4.40 (5H, br OH×5), 2.69 (1H, m), 2.78 (2H, m),2.90 (1.73H, s), 3.13 (1.27H, s), 3.30 (1H, m), 3.33 (1H, m), 3.72 (1H,m), 3.89 (1H, m), 4.13 (2H, s), 4.78 (0.67H, d, J=7.8 Hz), 5.00 (0.33H,d, J=8.3 Hz), 6.72-7.72 (9H, m). IR (KBr); υ 3350, 1760, 1640, 1600,1493, 1309, 1189 cm⁻¹. Mass (FAB); m/z 529 (M+H)+. Elementary Analysis:AS C₃₆H₄₂N₂O₁₁; Calcd.: C, 63.71; H, 6.24; N, 4.13. Found.: C, 63.51; H,6.37; N, 4.10.

Compound 141

mp 125-128° C. NMR (400 MHz, DMSO-d₆); δ 0.22 (2H, brs), 0.53 (2H, m),0.91 (1H, m), 1.3-1.7 (4H, m), 1.76 (2H, br s), 2.1-2.2 (2H, m), 2.21(1H, s), 2.35 (1H, m) 2.46 (1H, m), 2.6-2.8 (3H, m), 2.91 (2H, s), 3.15(1H, s), 3.2-3.9 (3H, m), 4.12 (1.4H, s), 4.75 (0.7H, d, J=7.3 Hz), 5.00(0.3H, d, J=8.3 Hz), 6.7-7.9 (2.7H, m), 7.36 (0.3H, d, J=15.6 Hz),7.5-7.7 (2H, m), 7.71 (1H, d, J=7.3 Hz), 7.80 (0.7H, d, J=7.8 Hz), 7.92(0.7H, s), 8.01 (0.3H, d, J=7.8 Hz), 8.14 (0.3H, s). IR(KBr); υ 3400,1765, 1648, 1605, 1336, 1127 cm⁻¹. Mass (FAB); m/z 597 (M+H). ElementaryAnalysis: As C₃₃H₃₅N₂O₅F₃.0.70(C₄H₆O₆).1.0H₂O; Calcd.: C, 59.74; H,5.77; N ,3.89; F, 7.92. Found.: C, 59.83; H, 5.82; N, 3.88; F, 7.88.

Example 13217-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-methoxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan.tartrate 142

245 mg of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan (free base of 1) obtained in example 11 was dissolved in 3.5ml of chloroform followed by the addition of an excess amount ofdiazomethane and stirring for 1 hour. After concentrating the reactionsystem, the residue was purified with silica gel column chromatography(20 g hexane/ethylacetate/methanol/aqueous ammonia=5/3/0.2/0.04) toobtain the free base of the target compound. After dissolving this inmethanol, 11 mg of tartaric acid was added to completely dissolvefollowed by concentration. The residue was re-precipitated from etherfollowed by filtration to obtain 83 mg of the target compound (yield:30%).

mp>115° C. (decomposition); NMR (400 MHz, DMSO-d₆+D20); δ 0.15-0.33 (2H,m), 0.48-0.63 (2H, m), 0.87-1.00 (1H, m), 1.05-1.55 (4H, m), 1.69-1.85(1H, m), 2.20-2.45 (2H, m), 2.55-2.95 (3H, m), 2.79 (0.9H, s), 2.94(2.1H, s), 3.08-3.22 (1H, m), 3.30-3.58 (2H, m), 3.78 (3H, s), 3.77 (1H,d, J=16.l Hz), 3.84 (1H, d, J=16.1 Hz), 4.09 (2H, s), 4.38-4.45 (0.3H,m), 4.55-4.63 (0.3H, m), 4.60 (0.7H, d, J=3.4 Hz), 4.88-4.96 (0.7H, m),6.68 (0.7H, d, J=8.3 Hz), 6.64-6.70 (0.3H, m), 6.86 (0.7H, d, J=8.3 Hz),6.82-6.88 (0.3H, m), 7.24 (0.7H, dd, J=8.3, 2.0 Hz), 7.24-7.30 (0.3H,m), 7.52 (0.7H, d, J=2.0 Hz), 7.52-7.56 (0.3H, m), 7.57 (0.7H, d, J=8.3Hz), 7.60 (0.3H, d, J=8.3 Hz). IR (KBr); υ 3324, 1628, 1402, 1309, 1267,1131 cm⁻¹. Mass (EI); m/z=556 M+. Elementary Analysis: AsC₃₀H₃₄N₂O₄Cl₂.0.87C₄H₆O₆.0.7H₂O; Calcd.: C 57.39; H 5.80; N 4.00; Cl10.12; Found.: C 57.35; H 5.91; N 4.09; Cl 10.19.

Example 13314β-Acetoxy-17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan.hydrochloride 143

443 mg of17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan (free base of 1) obtained in example 11 was dissolved inacetic anhydride followed by stirring for 1 hour at 160° C. with an oilbath. After concentrating the reaction solvent, the acetic anhydride wascompletely removed by azeotrope with toluene. The residue was dissolvedin 10 ml of methanol followed by the addition of 14 ml of 4% aqueoussulfuric acid and stirring for 18 hours. 10 ml of aqueous ammonia and 30ml of chloroform were then added to the system to separate, and theaqueous layer was extracted twice with 15 ml of chloroform. The organiclayer was concentrated after drying with anhydrous sodium sulfate andthe residue was purified with silica gel column chromatography (45g,chloroform/ethylacetate=2/1). This was then recrystallized fromchloroform and methanol followed by derivation of the crystals intohydrochloride with methanol solution of hydrochloride to obtain 299 mgof the target compound (yield: 59%).

mp>190° C. (decomposition); NMR (400 MHz, DMSO-d₆); δ 0.35-0.73 (4H, m),0.90-1.03 (1H, m), 1.05-1.75 (4H, m), 2.17 (2.25H, s), 2.24 (0.75H, s),2.30-2.62 (2H, m), 2.65-2.83 (1H, m), 2.80 (0.75H, s), 2.96 (2.25H, s),2.90-3.15 (2H, m), 3.18-3.52 (3H, m), 3.79 (0.75H, d, J=16.1 Hz), 3.84(0.75H, d, J=16.1 Hz), 3.93-4.07 (0.5H, m), 4.55-4.60 (0.25H, m), 4.72(0.75H, d, J=3.4 Hz), 4.77-4.85 (1H, m), 5.26 (1H, d, J=6.4 Hz), 6.50(0.25H, d, J=8.3 Hz), 6.61 (0.75H, d, J=8.3 Hz), 6.77 (1H, d, J=8.3 Hz),7.19-7.25 (0.25H, m), 7.24 (0.75H, dd, J=8.3, 2.0 Hz), 7.49 (0.25H, d,J=2.0 Hz), 7.52 (0.75H, d, J=2.0 Hz), 7.58 (0.75H, d, J=8.3 Hz), 7.60(0.25H, d, J=8.3 Hz), 9.20-9.47 (1H, m), 9.42 (0.25H, s), 9.43 (0.75H,s). IR (KBr); υ 3420, 1744, 1626, 1473, 1406, 1371, 1321, 1214, 1116,1035 cm⁻¹. Mass (EI); m/z 584 M+. Elementary Analysis: AsC₃₁H₃₄N₂O₅Cl₂.HCl.0.2H₂O; Calcd.: C, 59.52; H, 5.70; N, 4.48; Cl, 17.00.Found.: C, 59.40; H, 5.90; N, 4.56; Cl, 17.12.

Example 134

17-Cyclopropylmethyl-3-hydroxy-14β-acetoxy-4,5α-epoxy-6β-((N-methylcinnamamido)morphinan.tartrate144 (yield: 48%) was obtained by following the procedure of example 133but using17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methylcinnamamido)morphinan(free base of 6) instead of(7-cyclopropylmethy-4,5α-epoxy-3,4β-dihydroxy-6α-(N-methyl-3,4-dichlorophenylacetamido)morphinan (free base of 1).

mp 154-157° C. NMR (400 MHz, DMSO-d₆); δ 0.06 (2H, m), 0.42 (2H, d,J=8.3 Hz), 0.72 (1H, m), 1.2-1.4 (3H, m), 1.93 (1H, m), 2.05 (1H, m),2.11 (3H, s), 2.24 (1H, m), 2.37 (2H, m), 2.43 (1H, m), 2.62 (1H, m),2.89 (2H, s), 3.03 (1H, d, J=18.1 Hz), 3.15 (1H, s), 3.2-3.4 (1H, m),3.69 (0.7H, m), 4.15 (0.3H, m), 4.28 (1H, s), 4.70 (0.7H, d, J=7.8 Hz),4.82 (0.3H, d, J=8.3 Hz), 6.5-6.8 (3H, m), 7.1-7.5 (5.3H, m), 7.71(0.7H, d, J=6.3 Hz); IR (KBr); υ 3390, 1738, 1647, 1590, 1408, 1122cm⁻¹. Mass (FAB); m/z 529 (M+H). Elementary Analysis: AsC₃₂H₃₆N₂O₅.0.5(C₄H₆O₆).1.0H₂O; Calcd.: C, 65.68; H, 6.65; N, 4.50.Found.: C, 65.85; H, 6.66; N, 4.43.

Example 13517-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-aminocinnamamido)morphinan.hydrochloride145

360 mg of17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-nitrocinnamamido)morphiran(free base of 104) and 1.07 g of stannic chloride dihydrate wasdissolved in 7.5 ml of ethanol followed by heating to 70° C. andstirring for 2 hours. After cooling the reaction mixture to roomtemperature, 2 N aqueous sodium hydroxide was added while cooling withice to neutralize followed by extraction with dichloromethane. Theorganic layers were combined and washed with saturated brine. Afterdrying and concentrating, the organic substances were removed bychromatographic filtration [silica gel; chloroform:methanol (9:1)]. Theresulting crude target compound was converted into a dihydrochloride toobtain 310 mg.

Mass (FAB); m/z 502 ((M+H)+).

Example 13617-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-isothiocyanatocinnamamido)morphinanan.methanesulfonate146

300 mg of17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-aminocinnamamido)morphinan.hydrochloride145 obtained in example 135 was dissolved in 9 ml of water and cooledwith ice. 40 pl of thiophosgene dissolved in 2 ml of chloroform wasadded dropwise followed by stirring for 5 hours at warming to roomtemperature. Saturated aqueous sodium bicarbonate was then added toneutralize while cooling with ice followed by extraction withchloroform. The organic layers were combined and washed with saturatedbrine followed by drying and concentrating. The resulting residue waspurified with column chromatography [silica gel; chloroform:methanol(97.5:2.5)], to obtain 208 mg of the resulting target compound afterconverting a methanesulfonate from (yield: 52% 2 steps).

mp 170° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.42 (1H, m), 0.49(1H, m), 0.60 (1H, m), 0.69 (1H, m), 1.07 (1H, m), 1.27-1.58 (3H, m),1.72 (1H, m), 2.11 (1H, m), 2.31 (3H, s), 2.43-2.52 (2H, m), 2.86 (1H,m), 2.92 (2.1H, s), 3.02-3.14 (2H, m), 3.18 (0.9H, s), 3.30-3.38 (2H,m), 3.70 (0.7H, m), 3.83 (1H, m), 4.19 (0.3H, m), 4.80 (0.7H, d, J=8.3Hz), 4.90 (0.3H, d, J=8.3 Hz), 6.14 (0.3H, br s), 6.22 (0.7H, br s),6.65-6.84 (2.1H, m), 6.88 (0.7H, d, J=7.8 Hz), 7.29 (1H, d, J=15.6 Hz),7.40-7.50 (3.6H, m), 7.69 (0.3H, d, J=7.8 Hz), 7.91 (0.3H, s), 8.74 (1H,br s), 9.30 (0.3H, br s), 9.54 (0.7H, br s) IR (KBr); υ 3380, 3210,2124, 1649, 1599, 1197, 1060, 785 cm⁻¹. Mass (FAB); m/z 544 ((M+H)+);Elementary Analysis: As C₃₁H₃₃N₃O₄S.CH₃SO₃H.H₂O; Calcd. : C, 58.43; H,5.98; N, 6.39; S, 9.75; Found.: C, 58.67; H, 6.15; N, 6.11; S, 9.78.

Example 137

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-aminocinnamamido)morphinan.hydrochloride147 was obtained by following the procedure of example 135 but using17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-nitrocinnamamido)morphinan(free base of 97) instead of17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-nitrocinnamamido)morphinan(free base of 104).

Mass (FAB); m/z 502 ((M+H)+);

Examples 138-139

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-isothiocyanatocinnamamido)morphinan.methanesulfonate(yield: 32% 2 steps) 148 and17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-isothiocyanatophenylacetamido)morphinanan.methanesulfonate149 (yield: 78%) were obtained by following the procedure of example 136but using17-cyclopropyLmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-aminocinnamamido)morphinan.hydrochloride147 and17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-3-aminophenylacetamido)morphinan.hydrochloride138 instead of17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-3-aminocinnamamido)morphinan.hydrochloride145.

Compound 148

mp 160° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.41 (1H, m), 0.48(1H, m), 0.62 (1H, m), 0.70 (1H, m), 1.05 (1H, m), 1.20 (1H, m),1.40-1.67 (3H, m), 1.93 (1H, m), 2.31 (3.3H, s), 2.47 (1H, m), 2.71 (1H,m), 2.91 (0.6H, s), 2.93 (1H, m), 3.01-3.15 (2H, m), 3.10 (2.4H, s),3.25-3.38 (2H, m), 3.89 (1H, br d, J=5.9 Hz), 4.58 (0.2H, m), 4.73(0.8H, d, J=3.4 Hz), 4.94 (0.2H, br s), 5.04 (0.8H, m), 6.20 (0.8H, s),6.25 (0.2H, br s), 6.61 (1H, d, J=7.8 Hz), 6.72 (1H, d, J=7.8 Hz), 7.22(0.2H, d, J=14.1 Hz), 7.37 (0.8H, d, J=15.6 Hz), 7.42-7.54 (3H, m), 7.68(0.2H, d, J=7.3 Hz), 7.71 (0.8H, d, J=7.3 Hz), 7.77 (0.2H, s), 7.93(0.8H, s), 8.77 (1H, br s), 9.30 (1H, br s). IR (KBr); υ 3340, 3200,2112, 1649, 1599, 1508, 1460, 1210, 1195, 1118, 1060, 1038, 785 cm⁻¹.Mass (FAB); m/z 544 ((M+H)+). Elementary Analysis: AsC₃₁H₃₃N₃O₄S.1.1CH₃SO₃H.H₂O; Calcd.: C 57.77; H 5.95; N 6.29; S 10.09;Found.: C 57.72; H 6.04; N 6.22; S 10.22.

Compound 149

mp>155° C. (decomposition); NMR (500 MHz, DMSO-d₆); δ 0.38 (1H, m), 0.46(1H, m), 0.61 (1H, m), 0.70 (1H, m), 1.04 (1H, m), 1.15 (1H, m), 1.36(1H, m), 1.55 (1H, m), 1.62 (1H, m), 1.89 (1H, m), 2.30 (3H, s), 2.42(1H, m), 2.71 (1H, m), 2.93 (1H, m), 2.96 (3H, s), 3.03 (1H, m), 3.10(1H, m), 3.23-3.37 (2H, m), 3.73-3.90 (3H, m), 4.44 (0.1H, m)). 4.63(0.9H, d, J=3.7 Hz), 4.71 (0.1H, m), 4.98 (0.9H, ddd, J=14.3, 4.0, 4.0Hz), 6.12 (0.9H, s, OH), 6.23 (0.1H, s, OH), 6.59 (1H, d, J=8.3 Hz),6.71 (1H, d, J=8.3 Hz), 7.01-7.44 (4H, m), 8.75 (1H, m, NH+), 9.27 (1H,s, OH). IR (KBr); υ 3258, 2122, 1736, 1625, 1613, 1460, 1402, 1323,1207, 1160, 1120, 919, 775 cm⁻¹. Mass (FAB); m/z 532 ((M+H)+).Elementary Analysis: As C₃₀H₃₃N₃O₄S.CH₃SO₃H.0.9H₂O; Calcd.: C 57.82; H6.07; N 6.52; S 9.96; Found.: C 58.21; H 6.22; N 6.40; S 9.58.

Example 140 Opioid Activity Test Using the Isolated Guinea PigPreparation

A male Hartley guinea pig was used in this test. After sacrificing theguinea pig and extracting the ileum, the lumen was washed with nutrientsolution and only the longitudinal muscle was isolated. Thislongitudinal muscle was filled with Krebes-Henseleit solution (NaCl 118mM; KCl 4.7 mM; CaCl₂ 2.5 mM; KH₂PO₄ 1.2 mM; NaHCO₃ 25 MM; MgSO₄ 1.2 mMand glucose 10 mM) warmed to 37° C. and suspended in a Magnus tubeventilated with 5% carbon dioxide and 95% oxygen. Electrical stimuluswas performed at 0.1 Hz for 5.0 ms by means of ring-shaped platinumelectrodes located above and below. Tissue contractions were recorded ona polygraph using an isometric transducer.

Initially, the test drug was cumulatively added to a concentration atwhich specimen contractions caused by electrical stimulus weresuppressed by 50% to calculate the IC₅₀ value. Then after adequatelywashing with nutrient solution and the contraction reaction stabilized,naloxone, a μ agonist, or norBNI, a κ antagonist, were added and thetest compound was again cumulatively added after roughly 20 minutes. TheKe value was calculated using the following calculation formula from thedifference in the efficacies of both agonists.

Ke=[Conc. of added antagonist]/(IC₅₀ ratio−1)

IC₅₀ ratio=IC₅₀ in the presence of antagonist/IC₅₀ in the absence ofantagonist

As a result, when the ratio between the Ke value (μ) and Ke value (κ)was taken, Ke(μ)/Ke(κ)=4063. It was thus found that the compounds of thepresent invention are highly selective agonists for κ receptors.

Ke (nM) IC₅₀ (nM) Naloxone norBNI 1 0.026 650 0.16

Example 141 Opioid Activity Test Using the Isolated Mouse Vas DeferencePreparation

A male ddy mouse was used in this test. The isolated vas deference wasfilled with Krebes-Henseleit solution (NaCl 118 MM; KCl 4.7 mM; CaCl₂2.5 mM; KH₂PO₄ 1.1 mM; NaHCO₃ 25 mM; and glucose 10 mM) warmed to 37° C.and suspended in a Magnus tube ventilated with 5% carbon dioxide and 95%oxygen. Electrical stimulus was performed at 0.1 Hz for 5.0 ms by meansof ring-shaped platinum electrodes located above and below. Tissuecontractions were recorded on a polygraph using an isometric transducer.

Initially, the test drug was cumulatively added to a concentration atwhich specimen contractions caused by electrical stimulus weresuppressed by 50% to calculate the IC₅₀ value. Then after adequatelywashing with nutrient solution and the contraction reaction stabilized,naloxone, a μ antagonist, NTI, a δ antagonist, or norBNI, a κantagonist, were added and the test compound was again cumulativelyadded after roughly 20 minutes. The Ke value was calculated using thefollowing calculation formula from the difference in the efficacies ofboth agonists.

Ke=[Conc. of added antagonist]/(IC₅₀ ratio−1) $\begin{matrix}{{{IC}_{50}\quad {ratio}} = \quad {{IC}_{50}\quad {in}\quad {the}\quad {presence}\quad {of}\quad {{antagonist}/}}} \\{\quad {{IC}_{50}\quad {in}\quad {the}\quad {absence}\quad {of}\quad {antagonist}}}\end{matrix}$

A portion of the evaluation results of the compounds of the presentinvention are shown in Table 1. In each cases, there are no largedifferences in IC₅₀ values before and after use of naloxone, and agonistactivity by means of μ receptors was found to be extremely weak. Namely,compounds 24, 84, 96, 97, 126 are selective agonists for δ receptors,while compounds 1, 22, 38, 39, 42, 43, 45, 46, 47, 53, 57, 59, 60, 61,62, 63, 68, 69, 70, 73, 89, 91, 98, 99, 100, 101, 102, 103, 104, 122,140 and 141 are selective agonists for κ receptors.

TABLE 1 Opioid Activity of Compounds Ke IC₅₀ (nM) (nM) Naloxone NTInorBNI  1 0.395 53 17.3 0.548 22 1.20 800 545 5.53 24 0.121 16.5 0.4264.90 38 0.349 411 16.6 4.65 39 0.568 89.9 99.3 1.01 42 0.251 186 63.50.905 43 0.650 409 22.5 5.31 45 0.185 26.5 135 0.416 46 1.05 — — 0.44047 0.439 63.5 10.4 0.140 53 10.3 — 1676 0.21 57 0.0254 — 747 0.0124 591.14 21.3 47.3 0.151 60 0.468 — 291 3.20 61 0.420 14000 41.6 0.164 6214.7 — 90.2 0.203 63 0.746 60.9 96.9 1.60 68 0.457 5710 143 1.08 690.320 1780 64.5 1.95 70 0.545 — — 0.198 73 0.072 524 78 0.272 84 2.0735.4 0.309 5.69 89 0.0934 18.3 15.6 0.85 91 0.378 — 450 0.699 96 0.34632.5 1.61 4.21 97 0.247 163 2.92 13.9 98 1.30 — — 1.35 99 0.674 94.5 —0.652 100  0.647 1797 — 0.0717 101  0.269 25.4 31.6 0.0425 102  1.60 —276 2.37 103  11.0 — — 0.657 104  0.227 185 89 1.40 122  3.01 59.5 42.70.358 126  0.969 40.2 0.0065 1.20 140  0.413 320 261 1.06 141  0.160 142184 1.39

Example 142 Analgesic Activity Test Using the Acetic Acid-inducedWrithing Method

5 week old ddY mice were used in this test. After intraperitonealadministration of 0.1 ml of 0.6% aqueous acetic acid per 10 g of bodyweight, the number of writhing reactions that occurred in 10 minutesstarting 10 minutes after administration was evaluated for theindicator. The test drug was administered subcutaneously into the backsof the animals 15 minutes before administration of acetic acid. Aportion of those results are shown in Table 2. In this test, compounds42, 47, 63 and 96 demonstrating ED₅₀ values of 0.00136, 0.00052, 0.0011and 0.00086 mg/Kg, respectively, indicating particularly stronganalgesic activity.

TABLE 2 Analgesic Activity According to Acetic Acid Writhing ED₅₀ ED₅₀Compound (mg/kg) Compound (mg/kg)  1 0.017 22 0.0051 23 0.67 24 0.0057526 0.099 27 0.046 28 0.071 31 0.75 32 0.290 33 0.080 34 0.210 35 0.02636 0.23 37 0.0041 38 0.00352 39 0.0088 41 0.39 42 0.00136 43 0.0055 440.084 45 0.0038 46 0.013 47 0.00052 48 0.019 49 0.026 50 0.011 51 0.1953 0.46 54 0.72 55 0.980 56 0.00802 57 0.040 58 0.190 59 0.0028 600.0046 61 0.0044 62 0.077 63 0.0011 64 0.097 65 0.15 67 0.36 68 0.004269 0.0049 70 0.0016 71 0.0042 72 0.18 73 0.023 74 0.78 83 0.0080 840.0058 85 0.1128 86 0.0347 87 0.027 89 0.00471 91 0.019 94 0.013 950.0081 96 0.00086 97 0.0019 98 0.0068 99 0.0018 100  0.024 101  0.0066102  0.0019 103  0.069 104  0.017 105  0.098 106  0.25 107  0.023 108 0.0064 122  0.34 128  0.63 132  0.073 133  0.044 134  0.15 137  0.170138  0.014 139  0.040 140  0.0034 141  0.010 142  0.78 144  0.024 149 0.013 Morphine 0.55

Example 143 Evaluation of Diuretic Action

7-8 week old male Wistar rats were used in this test after prohibitingfrom drinking water for 1 hour before testing. After discharging anyurine accumulated in the bladder by gently stimulating the lowerabdomens of the animals, the drug was administered subcutaneously. After30 minutes, the animals were then forcibly given 20 ml/kg ofphysiological saline orally. The animals were then placed in metaboliccages immediately after administration of the drug (2 animals/cage) andurine output for 5 hours after loading with physiological saline wasmeasured. Drug efficacy was expressed in the form of those dosesresulting in urine outputs of 200 and 500, respectively, when the urineoutput of a non-dosed group was taken to be 100. Those doses wereexpressed as the ED₂₀₀ and ED₅₀₀ values, respectively. A portion ofthose results are shown in Table 3. In this test, the ED₂₀₀ values ofcompounds 22, 24, 42 and 43 were 0.00095, 0.00069, 0.00085 and 0.00054mg/kg, respectively, indicating that these compounds have extremelystrong diuretic action.

TABLE 3 Diuretic Action ED500 ED500 Compound ED200 (mg/kg) CompoundED200 (mg/kg)  1 0.0027 0.0457 22 0.00095 0.0170 24 0.00069 0.0063 270.0248 2.075 28 0.0200 3.799 35 0.0245 5.19 37 0.365 — 38 0.0038 0.28139 0.0041 0.228 42 0.00085 0.0061 43 0.00054 0.0044 45 0.0081 0.857 470.0016 — 50 0.0021 0.0325 53 0.135 0.658 56 0.0028 0.0518 57 0.04241.256 59 0.0105 2.364 60 0.0143 1.13 61 0.0032 0.157 62 0.101 7.04 630.0038 0.309 65 0.119 5.31 68 0.0016 0.0232 83 0.0261 2.99 84 0.00280.0469 86 0.0057 0.229 89 0.0012 0.0162 91 0.0094 0.960 95 0.0028 0.096896 0.0013 0.0549 97 0.0045 0.0939 98 0.0065 0.206 99 0.0011 0.0309 100 0.0159 0.811 101  0.0089 0.226 102  0.0014 0.0154 103  0.0827 5.65 105 0.0190 3.30 107  0.0061 0.20 108  0.0210 5.11 141  0.0319 3.45

Industrial Applicability

As a result of in vitro and in vivo tests, the compounds of the presentinvention were found to have both strong analgesic and diuretic activityas κ-agonists. It was clear that said compounds can be expected to beuseful as analgesics and diuretics. Based on the properties ofκ-agonists, the compounds of the present invention can also be used ashypotensives and sedatives.

What is claimed is:
 1. A morphinan derivative represented by formula (I)or its pharmacologically acceptable acid addition salt:

wherein, represents a single or double bond; R¹ represents an alkylgroup having 3 to 5 carbon atoms, a cycloalkylalky group having 4 to 7carbon atoms, an alkenyl group having 4 to 7 carbon atoms, or an allylgroup; R² represents a hydrogen atom, a hydroxy group, a straight-chainalkanoyloxy group having 1 to 5 carbon atoms, or a straight-chain alkoxygroup having 1 to 5 carbon atoms; R³ represents a hydrogen atom, ahydroxy group, an alkanoyloxy group having 1 to 5 carbon atoms or analkoxy group having 1 to 5 carbon atoms; A represents —NR^(4′)C(═Y)—,—NR^(4′)C(═Y)Z— or —NR^(4′)SO₂—; R^(4′) represents a straight-chain orbranched alkyl group having 1 to 5 carbon atoms or an aryl group having6 to 12 carbon atoms; Y and Z each independently represent NR⁴, S or O;R⁴ represents a hydrogen atom, a straight-chain or branched alkyl grouphaving 1 to 5 carbon atoms or an aryl group having 6 to 12 carbon atoms,and wherein each R⁴ may be identical or different; B represents (i) avalence bond, (ii) a straight-chain or branched alkylene group having 1to 14 carbon atoms which may be substituted with an alkoxy group having1 to 5 carbon atoms, an alkanoyloxy group having 1 to 5 carbon atoms, ora hydroxy group, (iii) a straight-chain or branched acyclic unsaturatedhydrocarbon radical having 1 to 3 double bonds and/or triple bonds andhaving 2 to 14 carbon atoms, or (iv) a straight-chain or branched chainsaturated or unsaturated hydrocarbon group having 1-14 carbon atoms andcontaining 1-5 heteroatom bonds selected from the group consisting ofthioether, ether and amino bonds, wherein no heteroatom is bondeddirectly to (A); R⁵ represents a hydrogen atom, or an organic grouphaving one of the following structures:

wherein the above structures may be substituted with one or more groupsselected from the group consisting of an alkyl group having 1 to 5carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a hydroxygroup, fluorine, chlorine, bromine, an amino group, a nitro group, acyano group, an isothiocyanate group, and a trifluoromethyl group; andR⁸ represents a hydrogen atom, a straight-chain alkyl group having 1 to5 carbon atoms or a straight-chain alkanoyl group having 1 to 5 carbonatoms; and formula (I) includes the (+) form, (−) form and (±) form;wherein said compound exhibits selective κ- or δ-opioid receptor agonistactivity.
 2. A compound according to claim 1 or a pharmacologicallyacceptable acid addition salt, wherein A represents —NR^(4′)(C═O)—,—NR^(4′)(C═S), —NR^(4′)(C═O)NR^(4′)—, —NR^(4′)(C═S)NR^(4′)—,—NR^(4′)(C═O)O— or —NR^(4′)SO₂— wherein R^(4′) has the same meaning asdefined above, and R^(4′) may be identical or different.
 3. A compoundaccording to claim 2 or a pharmacologically acceptable acid additionsalt thereof, wherein A represents —NR^(4′)C(═O)— wherein R^(4′) has thesame meaning as defined above.
 4. A compound according to claim 3 or itspharmacologically acceptable acid addition salt, wherein R¹ is acyclopropylmethyl, or allyl R² and R³ are independently a hydrogen atom,hydroxy, acetoxy or methoxy group, R⁴ is a methyl, ethyl, isopropylgroup, or isobutyl and R⁸ is a hydrogen atom or methyl group.
 5. Thecompound according to claim 4 or a pharamcologically acceptable acidaddition salt thereof, wherein B represents —(CH₂)_(n)—(n=0 to 6),—CH═CH—(CH₂)_(n)— (n=0 to 4), —CH≡CH—(CH₂)_(n)— (n=0 to 4), —CH₂—O—, or—CH₂—S—.
 6. The compound according to claim 5 or a pharmacologicallyacceptable salt thereof, having the formula:


7. The compound according to claim 1 or a pharmacologically acceptablesalt thereof, wherein R⁵ represents an organic group having one of thefollowing structures:

wherein the above structures may be substituted with one or more groupsselected from the group consisting of an alkyl group having 1 to 5carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a hydroxygroup, fluorine, chlorine, bromine, an amino group, a nitro group, acyano group, an isothiocyanate group, and a trifluoromethyl group. 8.The compound of claim 1, wherein B represents (i) a valence bond, (ii) astraight-chain or branched alkylene group having 1 to 14 carbon atomswhich may be substituted with an alkoxy group having 1 to 5 carbonatoms, an alkanoyloxy group having 1 to 5 carbon atoms, or a hydroxygroup, (iii) a straight-chain or branched acyclic unsaturatedhydrocarbon radical having 1 to 3 double bonds and/or triple bonds andhaving 2 to 14 carbon atoms, or (iv) a straight-chain or branchedsaturated hydrocarbon radical having one heteroatom bond selected fromthe group consisting of a thioether bond, an ether bond and an aminobond, wherein the total number of carbon atoms and heteroatom bonds is 2to 14 and no heteroatom is directly bonded to A.
 9. A pharmaceuticalcomposition comprising a pharmacologically effective amount of themorphinan derivative according to claim 1 or a pharmacologicallyacceptable acid addition salt thereof, and a pharmacologicallyacceptable carrier.
 10. A method for reducing pain, which comprisesadministering an effective analgesic amount of the morphinan derivativeaccording to claim 1 or a pharmacologically acceptable acid additionsalt thereof.
 11. A method for increasing the excretion of urine, whichcomprises administering an effective diuretic amount of the morphinanderivative represented by formula (I) or its pharmacologicallyacceptable acid addition salt thereof:

wherein represents a single or double bond; R¹, R², R³, R⁵, R⁸, A and Bare the same as defined in claim 1 and wherein said compound exhibitsκ-opioid agonist activity.